HCSGD entry for NFKB1
1. General information
| Official gene symbol | NFKB1 |
|---|---|
| Entrez ID | 4790 |
| Gene full name | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 |
| Other gene symbols | EBP-1 KBF1 NF-kB1 NF-kappa-B NF-kappaB NFKB-p105 NFKB-p50 NFkappaB p105 p50 |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0000122 | Negative regulation of transcription from RNA polymerase II promoter | IC IMP | biological_process |
| GO:0000975 | Regulatory region DNA binding | IDA | molecular_function |
| GO:0000976 | Transcription regulatory region sequence-specific DNA binding | IDA IEA | molecular_function |
| GO:0001071 | Nucleic acid binding transcription factor activity | IDA | molecular_function |
| GO:0001818 | Negative regulation of cytokine production | IEA | biological_process |
| GO:0002224 | Toll-like receptor signaling pathway | TAS | biological_process |
| GO:0002755 | MyD88-dependent toll-like receptor signaling pathway | TAS | biological_process |
| GO:0002756 | MyD88-independent toll-like receptor signaling pathway | TAS | biological_process |
| GO:0003690 | Double-stranded DNA binding | IEA | molecular_function |
| GO:0003700 | Sequence-specific DNA binding transcription factor activity | IEA | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005634 | Nucleus | IDA IEA | cellular_component |
| GO:0005654 | Nucleoplasm | TAS | cellular_component |
| GO:0005730 | Nucleolus | IDA | cellular_component |
| GO:0005737 | Cytoplasm | IDA | cellular_component |
| GO:0005739 | Mitochondrion | IDA | cellular_component |
| GO:0005829 | Cytosol | IEA TAS | cellular_component |
| GO:0006366 | Transcription from RNA polymerase II promoter | TAS | biological_process |
| GO:0006915 | Apoptotic process | IEA | biological_process |
| GO:0006954 | Inflammatory response | TAS | biological_process |
| GO:0006979 | Response to oxidative stress | IEA | biological_process |
| GO:0008134 | Transcription factor binding | IDA | molecular_function |
| GO:0009617 | Response to bacterium | IEA | biological_process |
| GO:0010744 | Positive regulation of macrophage derived foam cell differentiation | IC | biological_process |
| GO:0010884 | Positive regulation of lipid storage | IC | biological_process |
| GO:0010956 | Negative regulation of calcidiol 1-monooxygenase activity | IDA | biological_process |
| GO:0010957 | Negative regulation of vitamin D biosynthetic process | IC | biological_process |
| GO:0031072 | Heat shock protein binding | IEA | molecular_function |
| GO:0031293 | Membrane protein intracellular domain proteolysis | TAS | biological_process |
| GO:0032269 | Negative regulation of cellular protein metabolic process | IC | biological_process |
| GO:0032375 | Negative regulation of cholesterol transport | IC | biological_process |
| GO:0032481 | Positive regulation of type I interferon production | TAS | biological_process |
| GO:0033256 | I-kappaB/NF-kappaB complex | TAS | cellular_component |
| GO:0034134 | Toll-like receptor 2 signaling pathway | TAS | biological_process |
| GO:0034138 | Toll-like receptor 3 signaling pathway | TAS | biological_process |
| GO:0034142 | Toll-like receptor 4 signaling pathway | TAS | biological_process |
| GO:0034146 | Toll-like receptor 5 signaling pathway | TAS | biological_process |
| GO:0034162 | Toll-like receptor 9 signaling pathway | TAS | biological_process |
| GO:0034166 | Toll-like receptor 10 signaling pathway | TAS | biological_process |
| GO:0035666 | TRIF-dependent toll-like receptor signaling pathway | TAS | biological_process |
| GO:0038095 | Fc-epsilon receptor signaling pathway | TAS | biological_process |
| GO:0038123 | Toll-like receptor TLR1:TLR2 signaling pathway | TAS | biological_process |
| GO:0038124 | Toll-like receptor TLR6:TLR2 signaling pathway | TAS | biological_process |
| GO:0042803 | Protein homodimerization activity | IEA | molecular_function |
| GO:0043066 | Negative regulation of apoptotic process | IEA TAS | biological_process |
| GO:0043234 | Protein complex | IEA | cellular_component |
| GO:0044212 | Transcription regulatory region DNA binding | IDA | molecular_function |
| GO:0045083 | Negative regulation of interleukin-12 biosynthetic process | IEA | biological_process |
| GO:0045087 | Innate immune response | TAS | biological_process |
| GO:0045892 | Negative regulation of transcription, DNA-templated | IEA | biological_process |
| GO:0045893 | Positive regulation of transcription, DNA-templated | IDA IMP NAS | biological_process |
| GO:0045944 | Positive regulation of transcription from RNA polymerase II promoter | IEA | biological_process |
| GO:0046688 | Response to copper ion | IEA | biological_process |
| GO:0048011 | Neurotrophin TRK receptor signaling pathway | TAS | biological_process |
| GO:0050728 | Negative regulation of inflammatory response | IEA | biological_process |
| GO:0050852 | T cell receptor signaling pathway | TAS | biological_process |
| GO:0051092 | Positive regulation of NF-kappaB transcription factor activity | TAS | biological_process |
| GO:0071260 | Cellular response to mechanical stimulus | IEP | biological_process |
| GO:0071347 | Cellular response to interleukin-1 | IEP | biological_process |
| GO:0090263 | Positive regulation of canonical Wnt signaling pathway | IMP | biological_process |
| GO:1900127 | Positive regulation of hyaluronan biosynthetic process | IDA | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.0854197865 | 0.1245856806 | 0.6138613159 | 0.6776647448 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Down | -0.2366721692 |
| GSE13712_SHEAR | Down | -0.4191598502 |
| GSE13712_STATIC | Down | -0.2052733694 |
| GSE19018 | Down | -0.3793932545 |
| GSE19899_A1 | Down | -0.3743707872 |
| GSE19899_A2 | Up | 0.8886137184 |
| PubMed_21979375_A1 | Up | 1.2628592824 |
| PubMed_21979375_A2 | Up | 1.1000737289 |
| GSE35957 | Down | -0.1382725278 |
| GSE36640 | Down | -0.7835832863 |
| GSE54402 | Up | 0.6323009132 |
| GSE9593 | Up | 0.1768541509 |
| GSE43922 | Up | 0.4295192093 |
| GSE24585 | Down | -0.2801062228 |
| GSE37065 | Up | 0.2081314139 |
| GSE28863_A1 | Up | 0.5109939237 |
| GSE28863_A2 | Up | 0.3955636049 |
| GSE28863_A3 | Down | -0.4623377931 |
| GSE28863_A4 | Down | -0.2325860318 |
| GSE48662 | Down | -0.5634006944 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
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- Drugs
Name | Drug | Accession number |
|---|---|---|
| Pranlukast | DB01411 | - |
| HE3286 | DB05212 | - |
| P54 | DB05451 | - |
| NOX-700 | DB05464 | - |
| SGN-30 | DB05471 | - |
| CC-8490 | DB05487 | - |
| HMPL-004 | DB05767 | - |
| Triflusal | DB08814 | - |
- MicroRNAs
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-16-5p | MIMAT0000069 | MIRT006528 | ChIP-seq | Functional MTI (Weak) | 21081469 |
| hsa-miR-9-5p | MIMAT0000441 | MIRT003193 | qRT-PCR//Luciferase reporter assay//Western blot | Functional MTI | 19702828 |
| hsa-miR-9-5p | MIMAT0000441 | MIRT003193 | GFP reporter assay//qRT-PCR//Western blot | Functional MTI | 20102618 |
| hsa-miR-9-5p | MIMAT0000441 | MIRT003193 | GFP reporter assay//Western blot//EGFP reporter assay//qRT-PCR | Functional MTI | 22131135 |
| hsa-miR-9-5p | MIMAT0000441 | MIRT003193 | Reporter assay;Western blot | Functional MTI | 19289835 |
| hsa-miR-21-5p | MIMAT0000076 | MIRT006529 | ChIP-seq | Functional MTI (Weak) | 21081469 |
| hsa-miR-146a-5p | MIMAT0000449 | MIRT004459 | Luciferase reporter assay | Functional MTI | 18504431 |
| hsa-miR-146a-5p | MIMAT0000449 | MIRT004459 | qRT-PCR//Western blot | Functional MTI | 20124483 |
| hsa-miR-146a-5p | MIMAT0000449 | MIRT004459 | Microarray | Functional MTI (Weak) | 18660546 |
| hsa-miR-146b-5p | MIMAT0002809 | MIRT004530 | Luciferase reporter assay | Functional MTI | 18504431 |
| hsa-miR-15a-5p | MIMAT0000068 | MIRT004829 | Microarray//qRT-PCR | Functional MTI (Weak) | 17260024 |
| hsa-let-7a-5p | MIMAT0000062 | MIRT004830 | Microarray//qRT-PCR | Functional MTI (Weak) | 17260024 |
| hsa-miR-155-5p | MIMAT0000646 | MIRT021048 | Proteomics | Functional MTI (Weak) | 21030878 |
| hsa-miR-26b-5p | MIMAT0000083 | MIRT030242 | Microarray | Functional MTI (Weak) | 19088304 |
| hsa-miR-92a-3p | MIMAT0000092 | MIRT049105 | CLASH | Functional MTI (Weak) | 23622248 |
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- mirRecord
MicroRNA name | mirBase ID | Target site number | MiRNA mature ID | Test method inter | MiRNA regulation site | Reporter target site | Pubmed ID |
|---|---|---|---|---|---|---|---|
| hsa-miR-9-5p | MIMAT0000441 | 1 | hsa-miR-9 | {Western blot} | {downregulation by anti-miRNA oligonucleotide} | 19702828 |
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6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 136 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 27373322 | Oxidative stress plays a key role in driving COPD-related inflammation, even in ex-smokers, and might result in activation of the proinflammatory transcription factor nuclear factor kappaB (NF-kappaB), impaired antiprotease defenses, DNA damage, cellular senescence, autoantibody generation, and corticosteroid resistance though inactivation of histone deacetylase 2 |
| 27349869 | Additionally, Acrp30 stimulation suppresses NFkappaB p65, which induces abnormal expression of hBD-2 induced by H2O2 |
| 27168476 | These changes included a substantial induction in the nuclear factor NF-kappaB, a key inflammatory mediator |
| 27168476 | GPE cell treatment significantly protected the redox state and functional integrity of mitochondria, and counteracted senescence and NF-kappaB activation |
| 27114850 | Moreover, many stress-related signaling mechanisms, such as oxidative stress and energy metabolic disturbances, as well as the signaling cascades via ceramide, mTOR, NF-kappaB, and TGF-beta pathways, can also induce the expression of HIF-1alpha protein to facilitate cell survival in normoxia |
| 27101740 | Notably, the Egt beneficial effect was exerted through the upregulation of sirtuin 1 (SIRT1) and sirtuin 6 (SIRT6) expression and the downregulation of p66Shc and NF-kappaB |
| 27041570 | The transcription factor nuclear factor kappa B (NF-kappaB) and the long non-coding RNA (lncRNA) HOTAIR (HOX transcript antisense RNA) have diverse functional roles in cancer |
| 27041570 | We demonstrate that ectopic expression of HOTAIR induces NF-kappaB activation during DDR and interleukin-6 and interleukin-6 expression, both key NF-kappaB target genes |
| 27041570 | We show that HOTAIR regulates activation of NF-kappaB by decreasing Ikappa-Balpha (NF-kappaB inhibitor) and establish that by inducing prolonged NF-kappaB activation and expression of NF-kappaB target genes during DNA damage, HOTAIR has a critical role in cellular senescence and platinum sensitivity |
| 27015559 | Methylomic predictors demonstrate the role of NF-kappaB in old-age mortality and are unrelated to the aging-associated epigenetic drift |
| 27015559 | 5) CpG sites that mapped to genes functionally clustering around the nuclear factor kappa B (NF-kappaB) complex |
| 27015559 | Our results are in line with previous findings on the role of NF-kappaB in controlling animal life spans and demonstrate the role of this complex in human longevity |
| 26940461 | Calorie restriction-induced SIRT6 activation delays aging by suppressing NF-kappaB signaling |
| 26940461 | The transcription factor NF-kappaB, which is involved in inflammation and aging, has been shown to be regulated by SIRT6 |
| 26940461 | Moreover, SIRT6 overexpression is sufficient to delay the replicative senescence of WI38 by attenuating NF-kappaB signaling, while SIRT6 knockdown results in accelerated cell senescence and overactive NF-kappaB signaling |
| 26824319 | MITF expression was shown to be antagonized by the activation of transcription factor NF-kappaB |
| 26824319 | Parthenolide, an inhibitor of NF-kappaB, has not been yet reported to affect MITF-M expression |
| 26824319 | The mode of the response to parthenolide is bound to the molecular characteristics of melanoma cells, particularly to the basal MITF-M expression level but other cell-autonomous differences such as NF-kappaB activity and MCL-1 level might also contribute |
| 26824319 | Our data suggest that parthenolide can be developed as a drug used in combination therapy against melanoma when simultaneous inhibition of MITF-M, NF-kappaB and HDAC1 is needed |
| 26639398 | The effect of sirt6 overexpression on replicative senescence of chondrocytes and NF-kappaB target genes expression was evaluated |
| 26639398 | Meanwhile, the expression of NF-kappaB dependent genes were significantly attenuated by sirt6 overxpression |
| 26586398 | Moreover, irradiation induced expression of senescence-associated secretory phenotype (SASP) mRNAs and NFkappaB transcriptional activity in GBM cells |
| 26583757 | Inhibition of the NF-kappaB, p53, or Rb pathway proved insufficient to prevent kinase-triggered cell cycle arrest |
| 26498461 | Activation of nuclear factor-kappaB (NF-kappaB) in Burkitt's lymphoma (BL) and Hodgkin's lymphoma (HL) cells is important in the transformation and development process of these lymphomas |
| 26498461 | Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) and ligand-independent signaling by overexpressed CD30 are known to cause permanent activation of NF-kappaB in lymphomas |
| 26498461 | Here, we show that IkappaB-zeta, an inducible regulator of NF-kappaB, is constitutively expressed in BL and HL cell lines |
| 26498461 | Interestingly, IkappaB-zeta inhibited NF-kappaB activation by LMP-1 and CD30 |
| 26498461 | The results suggest that NF-kappaB-induced IkappaB-zeta negatively modulates NF-kappaB hyperactivation, resulting in a fine balance that ultimately endows a net evolutionary benefit to the survival of BL and HL cells |
| 26404840 | GATA4 in turn activates the transcription factor NF-kappaB to initiate the SASP and facilitate senescence |
| 26257076 | In addition, STIM1 and ORAI1 inhibited NF-kappaB signaling and remodeled the tumor microenvironment by reducing the formation of M2 phenotype macrophages, possibly creating an unfavorable tumor microenvironment and inhibiting cancer development |
| 26191269 | Quantitative PCR and Western blotting were used to detect the mRNA and protein expression of senescence regulatory molecules, such as SIRT6 and NF-kappaB |
| 26191269 | RESULTS: Compared with the aging group, the positive rate of SA-beta-gal staining cells and the proportion of cells in G1 phase decreased; the number of CFU-Mix increased; mRNA and protein expression of SIRT6 increased; mRNA and protein expression of NF-kappaB was down-regulated in Rg1 delaying and treatment groups; the changes of the indicators in Rg1 delaying group were more significant than those in Rg1 treatment group |
| 26147250 | Reduced IL1A diminished NF-kappaB transcriptional activity, which controls much of the SASP; exogenous IL1A restored IL6 secretion to rapamycin-treated cells |
| 26141949 | SIRT3 transcriptional activation is due to SIRT3 promoter activation controlled by the stress transcription factor NF-kappaB |
| 26112889 | Most of these data were derived from experimental findings in genetically modified mice, where NFkappaB, Pcsk9, low-density lipoprotein-receptor, PPARgamma, superoxide dismutase 2, poly[adenosine diphosphate-ribose] polymerase 1, and endothelial nitric oxide synthase were identified among others as crucial molecular targets and/or partners of sirtuins |
| 26105007 | Blocking LPS-induced NF-kappaB activation and cytokine production by Bay 11-7082 failed to rescue the impaired adipogenesis and the reduction in PPARgamma and Zfp423 expression |
| 26084179 | The mRNA and protein of senescence regulation molecules SIRT6 and NF-KB were examined by realtime fluorescence quantitative PCR (FQ-PCR) and western blotting |
| 26084179 | RESULT: Compared with the senescence group, the Rg1 anti-senescence group and the Rg1-treated group showed lower percentage in SA-beta-Gal-stained positive cells, decreased cell proportion in G1 phase, increased number of CFU-Mix, up-regulated in SIRT6 mRNA and protein expression, down-regulation in NF-KB mRNA and protein expression |
| 25847297 | Tat but not Nef induced an early increase in NF-kappaB activity and cytokine/chemokine secretion |
| 25847297 | Tat-induced effects were prevented by the NF-kappaB inhibitor parthenolide, indicating that Tat triggered senescence via NF-kappaB activation leading to oxidative stress |
| 25671639 | Inhibitors of NF-kappaB signaling and ceramide formation prevent methamphetamine-induced senescence and systemic inflammation in rats self-administering the drug, attenuating their health deterioration |
| 25655936 | Interestingly, it appears that NFkB, a critical inflammatory transcription factor, is sensitive to this age-related endothelial redox change and its activation induces transcription of pro-inflammatory cytokines that can further suppress endothelial function, thus creating a vicious feed-forward cycle |
| 25572145 | Re-expression of HPV16 E2 in SiHa (human cervical cancer) cells potentiates NF-kappaB activation induced by TNF-alpha concurrently increasing senescence and survival |
| 25572145 | In the present paper, we studied the effects of tumour necrosis factor (TNF)-alpha-mediated NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B-cells) activation on E2-induced senescence in HPV16-integrated SiHa cells |
| 25572145 | The results show that E2 inhibits endogenous E6 gene expression and sensitizes SiHa cells to TNF-alpha-induced NF-kappaB activation |
| 25572145 | Another observation in the present study is the significant up-regulation of key senescence messaging factors regulated by NF-kappaB namely interleukin (IL)-6, IL-8, high-mobility group protein A (HMGA)1 and B (HMGB)1 in E2-transfected cells treated with TNF-alpha |
| 25553648 | Loss of Nfkb1 leads to early onset aging |
| 25553648 | NF-kappaB is a major regulator of age-dependent gene expression and the p50/NF-kappaB1 subunit is an integral modulator of NF-kappaB signaling |
| 25553648 | Here, we examined Nfkb1-/- mice to investigate the relationship between this subunit and aging |
| 25553648 | Although Nfkb1-/- mice appear similar to littermates at six months of age, by 12 months they have a higher incidence of several observable age-related phenotypes |
| 25553648 | In addition, aged Nfkb1-/- animals have increased kyphosis, decreased cortical bone, increased brain GFAP staining and a decrease in overall lifespan compared to Nfkb1+/+ |
| 25553648 | In vitro, serially passaged primary Nfkb1-/- MEFs have more senescent cells than comparable Nfkb1+/+ MEFs |
| 25553648 | Also, Nfkb1-/- MEFs have greater amounts of phospho-H2AX foci and lower levels of spontaneous apoptosis than Nfkb1+/+, findings that are mirrored in the brains of Nfkb1-/- animals compared to Nfkb1+/+ |
| 25553648 | Together, these data show that loss of Nfkb1 leads to early animal aging that is associated with reduced apoptosis and increased cellular senescence |
| 25553648 | These findings support the strong link between the NF-kappaB pathway and mammalian aging |
| 25536232 | NEMO modulates radiation-induced endothelial senescence of human umbilical veins through NF-kappaB signal pathway |
| 25536232 | Electrophoretic mobility shift assay (EMSA) showed that pretreatment with PS1145 inhibited the radiation-induced NF-kappaB activation, which regulates cell fate in response to genotoxic stress |
| 25407919 | NF-kappaB is one of the major transcription factors mediating the induction of E-selectin and VCAM-1 expression, adhesion molecules responsible for leucocyte attachment to EC |
| 25407919 | TNFalpha-induced activation of NF-kappaB was suppressed in ARHGAP18-induced senescent EC, and this inhibition was reversed by Caveolin-1 knock-down |
| 25331947 | Here we show that cisplatin treatment of head and neck cancer cells results in nuclear transport of p16 leading to a molecular modification of NFkappaB |
| 25331947 | Chromatin immunoprecipitation assays show that this modification is associated with the inhibition of NFkappaB interacting with its DNA binding sequences, leading to decreased expression of NFkappaB-transcribed proteins |
| 25331947 | Furthermore, we have observed increased NFkappaB ubiquitination with cisplatin treatment that is abolished in the absence of p16 and gigaxonin expression |
| 25331947 | These results clearly demonstrate that nuclear p16 and gigaxonin play an important role in chemosensitivity of head and neck cancers through ubiquitination of NFkappaB |
| 25255445 | Regulation of p53 and Rb links the alternative NF-kappaB pathway to EZH2 expression and cell senescence |
| 25255445 | Moreover, our ChIP analysis demonstrates that EZH2 is also a direct NF-kappaB target gene |
| 25255445 | We show that this pathway provides the major route of crosstalk between the alternative NF-kappaB pathway and p53, a consequence of which is to suppress cell senescence |
| 25255445 | Importantly, we find that activation of NF-kappaB also induces EZH2 expression in CD40L stimulated cells from Chronic Lymphocytic Leukemia patients |
| 25255445 | We therefore propose that this pathway provides a mechanism through which microenvironment induced NF-kappaB can inhibit tumor suppressor function and promote tumorigenesis |
| 25246106 | Klotho Prevents NFkappaB Translocation and Protects Endothelial Cell From Senescence Induced by Uremia |
| 25018007 | Loss of HuR leads to senescence-like cytokine induction in rodent fibroblasts by activating NF-kappaB |
| 25018007 | The induction of SASP factors did not depend on ARF-p53 pathway-mediated cell cycle arrest, but required NF-kappaB activity |
| 25018007 | In the absence of HuR, cells were defective in the DNA-damage response, and single strand DNA breaks accumulated, which may have caused the activation of NF-kappaB and subsequent cytokine induction |
| 24960204 | Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-kappaB induces premature ageing in mice |
| 24828530 | PKD1 is activated by oncogenic Ras expression and PKD1 promotes Ras OIS by mediating inflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) via modulation of NF-kappaB activity |
| 24721210 | Furthermore, HDIs activate Gadd45alpha/NF-kappaB signaling pathway to suppress apoptosis thereby promoting the cell survival |
| 24713059 | These analyses suggest a role for Akt, nuclear factor-kappaB (NF-kappaB), heat shock protein 90 (HSP90), p70/p80 autoantigen, 14-3-3 proteins, and dynein in telomere functions |
| 24674756 | PPM1B is a member of the protein phosphatase 2C family and plays a role in negatively regulating p53 and NF-kappaB thereby possibly attenuating the gene expression program of cellular senescence |
| 24608805 | The NF-kappaB pathway transcriptionally controls a large set of target genes that play important roles in cell survival, inflammation, and immune responses |
| 24608805 | While many studies showed anti-tumorigenic and pro-survival role of NF-kappaB in cancer cells, recent findings postulate that NF-kappaB participates in a senescence-associated cytokine response, thereby suggesting a tumor restraining role of NF-kappaB |
| 24608805 | In this review, we discuss implications of the NF-kappaB signaling pathway in cancer |
| 24608805 | Particularly, we emphasize the connection of NF-kappaB with cellular senescence as a response to chemotherapy, and furthermore, present examples how distinct oncogenic network contexts surrounding NF-kappaB produce fundamentally different treatment outcomes in aggressive B-cell lymphomas as an example |
| 24599132 | This review summarizes recent insights to the noncanonical functions of telomerase reverse transcriptase (TERT) catalytic subunit, in particular in cancer progression, and highlights two major signaling mechanisms involved in the cross-talk with TERT-the NF-kappaB and Wnt/beta-catenin pathways |
| 24403591 | NF-kappaB inhibition facilitates the establishment of cell lines that chronically produce human T-lymphotropic virus type 1 viral particles |
| 24403591 | When NF-kappaB activity is blocked by a degradation-resistant form of IkappaBalpha, DeltaN-IkappaBalpha, Tax-induced senescence is averted |
| 24403591 | Here, we show that NF-kappaB inhibition through the expression of DeltaN-IkappaBalpha allows cells of a human osteosarcoma (HOS) cell line to be chronically infected by HTLV-1 |
| 24403591 | The ease with which chronic and productive HTLV-1 infection can be established in cell culture through inhibition of NF-kappaB affords a useful means to examine in depth the molecular events of HTLV-1 replication and the mechanisms of action of viral genes |
| 24400224 | Recent studies have elucidated roles for NF-kappaB, STAT3 and JNK as possible missing links |
| 24337384 | We identified a conserved TNFR-associated factor 6 (TRAF6) binding motif, which was required for CD158d-induced NF-kappaB activation and IL-8 secretion, TRAF6 association with CD158d, and TRAF6 recruitment to CD158d(+) endosomes in transfected cells |
| 24270409 | Sprouty1 induces a senescence-associated secretory phenotype by regulating NFkappaB activity: implications for tumorigenesis |
| 24270409 | In vivo analysis of thyroid glands from Spry1 knockout mice reveals that Spry1 induces a senescence-associated secretory phenotype via activation of the NFkappaB pathway |
| 24057048 | In sarcomatoid cell lines Co-ASS was more potent than Co-EPM and the prototypal metallo-drug cisplatin, and induced cell death through the intrinsic apoptotic pathway, associated with a strong NF-kappaB inhibition |
| 24043947 | The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) proteins are a family of ubiquitously expressed transcription factors that regulate the response to cellular stress |
| 24043947 | However, recent studies have now revealed that NF-kappaB can also function as a tumor suppressor through the induction of cellular senescence |
| 24043947 | Herein, we review the evidence indicating a role for NF-kappaB in tumor suppression via cellular senescence and suggest that depending upon the subunit expressed, the biological context, and the type and intensity of the signal, NF-kappaB can indeed promote senescence growth arrest |
| 23805154 | The inhibitory action probably relates to the need for activating anti-inflammatory mechanisms to counter potent proinflammatory signals, like the nuclear factor kappaB (NF-kappaB) pathway, to prevent cell and tissue destruction |
| 23781024 | Here, we show that IkappaBzeta, an atypical member of the inhibitor of NFkappaB proteins and selective coactivator of particular NFkappaB target genes, is an important regulator of SASP expression |
| 23727324 | LPS-induced NF-kappaB activation diminished after CoQ10H(2) pretreatment in both young and senescent cells |
| 23688930 | MicroRNAs (miRs), a class of molecules involved in gene expression regulation, are emerging as modulators of some pathways, including NF-kappaB, mTOR, sirtuins, TGF-beta and Wnt, that may be related to inflammation, cellular senescence and age-related diseases, cancer included |
| 23688930 | Here we review recent findings concerning three of them, miR-21, -126 and -146a, which target mRNAs belonging to the NF-kappaB pathway; we discuss their ability to link cellular senescence, inflamm-aging and cancer and their changes in centenarians, and provide an update on the possibility of using miRs to block accumulation of senescent cells to prevent formation of a microenvironment favoring cancer development and progression |
| 23649808 | HMGB1 depletion, HMGB1 blocking antibody, or TLR-4 inhibition attenuated senescence-associated IL-6 secretion, and exogenous HMGB1 stimulated NF-kappaB activity and restored IL-6 secretion to HMGB1-depleted cells |
| 23624226 | NF-kappaB activity was determined by Western blot |
| 23578198 | Taken together, our findings suggested that sunitinib treatment performance could be attributable to TIS, depending on p53/Dec1 activation via inhibited Raf-1/nuclear factor (NF)-kappaB activity |
| 23542362 | In this review, the mechanisms of cigarette smoke/oxidant-mediated redox posttranslational modifications of SIRT1 and its roles in PARP1 and NF-kappaB activation, and FOXO3 and eNOS regulation, as well as chromatin remodeling/histone modifications during inflammaging, are discussed |
| 23521863 | Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-kappaB activation |
| 23521863 | Bioinformatic analysis of genes downregulated by metformin suggests that the drug blocks the activity of the transcription factor NF-kappaB |
| 23521863 | In agreement, metformin prevented the translocation of NF-kappaB to the nucleus and inhibited the phosphorylation of IkappaB and IKKalpha/beta, events required for activation of the NF-kappaB pathway |
| 26201620 | Examples include the HLA class-II region and genes implicated in IL12-JAK/STAT signaling, and the NF-kappaB and TNF signaling pathways |
| 23281008 | This leads to enhanced secretion of inflammatory cytokines known to drive osteoclastogenesis, such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and receptor activator of NF-kappaB ligand (RANKL), and thereby induces an inflammatory bone microenvironment favoring osteoclastogenesis |
| 23281008 | Furthermore, we found that the transcription factor NF-kappaB is activated in osteoblastic and osteoclastic cells of the Ercc1 mutant mice |
| 23281008 | Finally, pharmacological inhibition of the NF-kappaB signaling via an I-kappaB kinase (IKK) inhibitor reversed cellular senescence and SASP in Ercc1(-/Delta) BMSCs |
| 23281008 | Therefore, the NF-kappaB pathway represents a novel therapeutic target to treat aging-related bone disease |
| 23272171 | DEX co-treatment cells exhibited the decrease of DNA damage signaling pathway proteins, the lower expression of p53 and p21(CIP1), the lower cellular secretory program and down-regulation of NF-kappaB and its signaling cascade |
| 23264905 | Senescence and NFkappaB: A trojan horse in tumors |
| 23264905 | Here we discuss recent findings regarding the role of NFkappaB in the modulation of the SASP and the consequent anticancer immune response |
| 23220384 | Suppression of autophagocytosis provokes inflammation including NF-kappaB activation which further potentiates anti-apoptotic defence |
| 23193674 | Recent studies show that through adjusting the activity of endothelial nitric oxide syntheses (eNOS), p53, forkhead box class O (FOXO) and nuclear factor kappa B (NF-kappaB), SIRT1 can protect the functions of vascular endothelia and nerves in a variety of pathological conditions |
| 23184984 | CD158d initiates signaling through DNA-PKcs, Akt, and NF-kappaB for a proinflammatory and proangiogenic response |
| 23180582 | Targeting aurora kinases limits tumour growth through DNA damage-mediated senescence and blockade of NF-kappaB impairs this drug-induced senescence |
| 23180582 | Blockade of IKKbeta/NF-kappaB led to reversal of MLN8237-induced senescence and SASP |
| 23159434 | Furthermore, the overexpression of PGC-1alpha induced by transfection largely increased the expression levels of NRF-1 and TFAM and significantly decreased the expression level of NF-kappaB in the cell senescence model |
| 23047866 | Pharmacologic or antibody-mediated blockade of NF-kappaB or alphavbeta3 was sufficient to inhibit alpha-catulin-induced cell migration and invasion |
| 22899934 | Emerging studies have indicated that the IKK/NF-kappaB signaling axis regulates autophagy in a context-dependent manner |
| 22899934 | IKK complex and NF-kappaB can enhance the expression of Beclin 1 and other autophagy-related proteins and stimulate autophagy whereas as a feedback response, autophagy can degrade IKK components |
| 22899934 | Moreover, NF-kappaB signaling activates the expression of autophagy inhibitors (e |
| 22899934 | Several studies have indicated that NF-kappaB signaling is enhanced both during aging and cellular senescence, inducing a proinflammatory phenotype |
| 22899934 | We will review the recent literature on the control mechanisms of autophagy through IKK/NF-kappaB signaling and emphasize that NF-kappaB signaling could be a potent repressor of autophagy with ageing |
| 22864395 | Significantly, higher IFNbeta and chemokine gene transcripts have been observed, together with increased STAT1 and decreased STAT3 and NF-kappaB signaling activities |
| 22789011 | Furthermore, hPTTG1 overexpression activated NF-kappaB signaling to transactivate the expression of interleukin (IL)-8 and growth-regulated oncogene alpha (GROalpha) to execute CXCR2 signaling in MCF-7 cells |
| 22740410 | HTLV-1 tax-induced rapid senescence is driven by the transcriptional activity of NF-kappaB and depends on chronically activated IKKalpha and p65/RelA |
| 22740410 | The HTLV-1 oncoprotein Tax is a potent activator of classical and alternative NF-kappaB pathways and is thought to promote cell proliferation and transformation via NF-kappaB activation |
| 22740410 | We showed recently that hyperactivation of NF-kappaB by Tax triggers a cellular senescence response (H |
| 22740410 | Inhibition of NF-kappaB activation by expression of I-kappaBalpha superrepressor or by small hairpin RNA (shRNA)-mediated knockdown of p65/RelA rescues cells from Tax-induced rapid senescence (Tax-IRS) |
| 22740410 | Here we demonstrate that Tax-IRS is driven by the transcriptional activity of NF-kappaB |
| 22740410 | Consistent with a critical role of IKKalpha in the transcriptional activity of NF-kappaB, IKKalpha deficiency drastically decreased NF-kappaB trans-activation by Tax, although it only modestly reduced Tax-mediated I-kappaBalpha degradation and NF-kappaB nuclear localization |
| 22740410 | In contrast, although IKKbeta knockdown attenuated Tax-induced NF-kappaB transcriptional activation, the residual NF-kappaB activation in IKKbeta-deficient cells was sufficient to trigger Tax-IRS |
| 22740410 | In the presence of Tax, the delineation between the classical and alternative NF-kappaB pathways becomes obscured |
| 22740410 | The senescence checkpoint triggered by Tax is driven by the transcriptional activity of NF-kappaB, which depends on activated IKKalpha and p65/RelA |
| 22718354 | RB family, and in particular the most studied member RB/p105, has been considered a tumor suppressor gene by more than three decades, and numerous efforts have been done to understand his molecular activity |
| 22706308 | NF-kappaB inhibition delays DNA damage-induced senescence and aging in mice |
| 22706308 | NF-kappaB, a transcription factor activated by cellular damage and stress, has increased activity with aging and aging-related chronic diseases |
| 22706308 | To determine whether NF-kappaB drives aging in response to the accumulation of spontaneous, endogenous DNA damage, we measured the activation of NF-kappaB in WT and progeroid model mice |
| 22706308 | As both WT and progeroid mice aged, NF-kappaB was activated stochastically in a variety of cell types |
| 22706308 | Genetic depletion of one allele of the p65 subunit of NF-kappaB or treatment with a pharmacological inhibitor of the NF-kappaB-activating kinase, IKK, delayed the age-related symptoms and pathologies of progeroid mice |
| 22706308 | Additionally, inhibition of NF-kappaB reduced oxidative DNA damage and stress and delayed cellular senescence |
| 22706308 | These results indicate that the mechanism by which DNA damage drives aging is due in part to NF-kappaB activation |
| 22706308 | IKK/NF-kappaB inhibitors are sufficient to attenuate this damage and could provide clinical benefit for degenerative changes associated with accelerated aging disorders and normal aging |
| 22673730 | NF-kappaB accumulation associated with COL1A1 transactivators defects during chronological aging represses type I collagen expression through a -112/-61-bp region of the COL1A1 promoter in human skin fibroblasts |
| 22673730 | On the other hand, the aging process was accompanied by elevated amounts and binding activities of NF-kappaB (p65 and p50 subunits), together with an increased number of senescent cells |
| 22673730 | The forced expression of NF-kappaB performed in young fibroblasts was able to establish an old-like phenotype by repressing COL1A1 expression through the short -112/-61-bp COL1A1 promoter and by elevating the senescent cell distribution |
| 22658522 | Selective autophagy of the adaptor protein Bcl10 modulates T cell receptor activation of NF-kappaB |
| 22658522 | Bcl10 degradation is a poorly understood biological phenomenon suggested to reduce TCR activation of NF-kappaB |
| 22658522 | Blockade of Bcl10 autophagy enhanced TCR activation of NF-kappaB |
| 22658522 | Together, these data demonstrate that selective autophagy of Bcl10 is a pathway-intrinsic homeostatic mechanism that modulates TCR signaling to NF-kappaB in effector T cells |
| 22658522 | This homeostatic process may protect T cells from adverse consequences of unrestrained NF-kappaB activation, such as cellular senescence |
| 22546858 | Inhibition of lung inflammation by an NF-kappaB/IKK2 inhibitor did not have any beneficial effect on emphysema |
| 22404905 | Suppression of the prototypical SASP component IL-6 required the glucocorticoid receptor, which, in the presence of ligand, inhibited IL-1alpha signaling and NF-kappaB transactivation activity |
| 22404905 | Accordingly, co-treatments combining glucocorticoids with the glucocorticoid antagonist RU-486 or recombinant IL-1alpha efficiently reestablished NF-kappaB transcriptional activity and IL-6 secretion |
| 22396894 | NF-kappaB in Aging and Disease |
| 22396894 | The IKK/NF-kappaB signaling pathway has been proposed to be one of the key mediators of aging |
| 22396894 | Transcriptional activity of NF-kappaB is increased in a variety of tissues with aging and is associated with numerous age-related degenerative diseases including Alzheimer's, diabetes and osteoporosis |
| 22396894 | In mouse models, inhibition of NF-kappaB leads to delayed onset of age-related symptoms and pathologies |
| 22396894 | In addition, NF-kappaB activation is linked with many of the known lifespan regulators including insulin/IGF-1, FOXO, SIRT, mTOR, and DNA damage |
| 22396894 | Thus NF-kappaB represents a possible therapeutic target for extending mammalian healthspan |
| 22390170 | Silencing of the DEK gene induces apoptosis and senescence in CaSki cervical carcinoma cells via the up-regulation of NF-kappaB p65 |
| 22390170 | In the present study, DEK and IkappaBalpha [inhibitor of NF-kappaB (nuclear factor kappaB) alpha] shRNAs (short hairpin RNAs) were constructed and transfected into CaSki cells using Lipofectamine |
| 22390170 | The intracellular expression of NF-kappaB p65 protein was studied by cytochemistry |
| 22390170 | In addition, the NF-kappaB p65 DNA-binding activity was measured by ELISA |
| 22390170 | All of these effects may be related to the up-regulation of NF-kappaB p65 expression and its nuclear translocation |
| 22267761 | The lung tissue in which type II cells contained higher numbers of gammaH2AX foci per cell had higher percentages of type II cells that expressed p16(INK4a) (p16), phosphorylated nuclear factor (NF)-kappaB and interleukin (IL)-6, and of alveolar wall cells that expressed active caspase-3 |
| 22267761 | The type II cells that contained higher numbers of gammaH2AX foci per cell had higher rates of expression of p16, phosphorylated NF-kappaB, and IL-6 |
| 22182507 | Emerging role of NF-kappaB signaling in the induction of senescence-associated secretory phenotype (SASP) |
| 22182507 | Emerging data has revealed that NF-kappaB signaling is the major signaling pathway which stimulates the appearance of SASP |
| 22182507 | On the other hand, two cyclin-dependent kinase inhibitors, p16INK4a and p14ARF, are effective inhibitors of NF-kappaB signaling |
| 22182507 | We will review in detail the signaling pathways which activate NF-kappaB signaling and trigger SASP in senescent cells |
| 22095030 | Nevertheless, regulation of other pathways which are not relevant to p53, yet important for tumorigenesis such as TGF-beta and NF-kappaB, by ING proteins is also observed |
| 22074157 | Pentoxifylline sensitizes human cervical tumor cells to cisplatin-induced apoptosis by suppressing NF-kappa B and decreased cell senescence |
| 22074157 | CONCLUSION: PTX sensitizes cervical cancer cells to CIS-induced apoptosis and decreases the CIS-induced senescence in these cells via inhibition of NF-kappaB signaling pathway; diminishes expression of antiapoptotic proteins and the activation of caspases |
| 21990145 | This research perspective focuses on the evidence for a functional relationship between NF-kappaB and senescence, and how disruption of the NF-kappaB pathway can lead to its bypass |
| 21982118 | Even though there were lower basal levels of NF-kappaB activity in the PC-3 D12 cells compared to the Parental PC-3, docetaxel induced higher NF-kappaB activity and IkappaB phosphorylation at 3 and 6 hours with only minor changes in the DU-145 cells |
| 21982118 | Inhibition of NF-kappaB with the BAY 11-7082 inhibitor reversed the resistance to Docetaxel |
| 21982118 | CONCLUSION: This study confirms that multiple mechanisms contribute to Docetaxel resistance and the central transcription factor NF-kappaB plays an immensely important role in determining docetaxel-resistance which may represent an appropriate therapeutic target |
| 21979375 | Control of the senescence-associated secretory phenotype by NF-kappaB promotes senescence and enhances chemosensitivity |
| 21979375 | We found that NF-kappaB acts as a master regulator of the SASP, influencing the expression of more genes than RB and p53 combined |
| 21979375 | In cultured fibroblasts, NF-kappaB suppression causes escape from immune recognition by natural killer (NK) cells and cooperates with p53 inactivation to bypass senescence |
| 21979375 | In a mouse lymphoma model, NF-kappaB inhibition bypasses treatment-induced senescence, producing drug resistance, early relapse, and reduced survival |
| 21979375 | Our results demonstrate that NF-kappaB controls both cell-autonomous and non-cell-autonomous aspects of the senescence program and identify a tumor-suppressive function of NF-kappaB that contributes to the outcome of cancer therapy |
| 21832251 | NF-kappaB plays an important role in indoxyl sulfate-induced cellular senescence, fibrotic gene expression, and inhibition of proliferation in proximal tubular cells |
| 21832251 | However, little is known about the role of nuclear factor (NF)-kappaB in these processes |
| 21832251 | Indoxyl sulfate induced phosphorylation of NF-kappaB p65 on Ser-276, which was suppressed by N-acetylcysteine, an antioxidant |
| 21832251 | Furthermore, indoxyl sulfate induced NF-kappaB p65 expression |
| 21832251 | Inhibitors of NF-kappaB (pyrrolidine dithiocarbamate and isohelenin) and NF-kappaB p65 small interfering RNA (siRNA) suppressed indoxyl sulfate-induced senescence-associated beta-galactosidase activity and expression of p53, transforming growth factor (TGF)-beta1, and alpha-smoothe muscle actin (SMA) |
| 21832251 | NF-kappaB inhibitors suppressed indoxyl sulfate-induced p21 expression, whereas NF-kappaB p65 siRNA enhanced its expression |
| 21832251 | NF-kappaB inhibitors partially alleviated indoxyl sulfate-induced inhibition of cellular proliferation |
| 21832251 | NF-kappaB p65 siRNA-transfected cells showed less proliferation in the presence of indoxyl sulfate than control cells |
| 21832251 | Taken together, NF-kappaB plays an important role in indoxyl sulfate-induced cellular senescence, fibrotic gene expression, and inhibition of proliferation in proximal tubular cells |
| 21779477 | Accordingly, Pml(-/-) mice are resistant to lipopolysaccharide (LPS)-induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-kappaB prosurvival pathway |
| 21740549 | Although none of them has previously been linked to cellular senescence, TMEM9B has been suggested to be an upstream activator of NF-kappaB signalling which has been found to have a causal role in promoting senescence |
| 21738489 | Sirt6 can interact with the stress-responsive transcription factor NF-kappaB and regulate some NF-kappaB target genes, but the full scope of Sirt6 target genes as well as dynamics of Sirt6 occupancy on chromatin are not known |
| 21738489 | These data suggest dynamic chromatin relocalization of Sirt6 as a key output of NF-kappaB signaling in stress response and aging |
| 21698300 | Compared to early cultures, late passage HUVECs also exhibited nuclear translocation of NF-kappaB (p65) and reciprocal shifts in BAX and BCL2 protein content resulting in almost 2-fold increase in BAX/BCL2 ratio and 3-fold increase in apoptotic response to TNFalpha exposure (p<0 |
| 21627565 | HER2 was found to mediate hTERT expression through activation of Nuclear Factor-kappa B (NF-kappaB) and c-myc |
| 21627565 | CONCLUSIONS: The present study suggests that following irradiation, HER2 receptor activates hTERT/telomerase, increasing the breast cancer cells' survival potential, through sequential induction of transcription factors NF-kappaBeta and c-myc |
| 21552325 | NF-kappaB hyper-activation by HTLV-1 tax induces cellular senescence, but can be alleviated by the viral anti-sense protein HBZ |
| 21552325 | Activation of I-kappaB kinases (IKKs) and NF-kappaB by the human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, is thought to promote cell proliferation and transformation |
| 21552325 | Here we demonstrate that p21(CIP1/WAF1)-/p27(KIP1)-mediated senescence constitutes a checkpoint against IKK/NF-kappaB hyper-activation |
| 21552325 | Senescence induced by Tax in HeLa cells is attenuated by mutations in Tax that reduce IKK/NF-kappaB activation and prevented by blocking NF-kappaB using a degradation-resistant mutant of I-kappaBalpha despite constitutive IKK activation |
| 21552325 | Finally, we show that down-regulation of NF-kappaB by the HTLV-1 anti-sense protein, HBZ, delay or prevent the onset of Tax-induced senescence |
| 21552325 | Robust HTLV-1 replication and elevated Tax expression drive IKK/NF-kappaB hyper-activation and trigger senescence |
| 21552325 | HBZ, however, modulates Tax-mediated viral replication and NF-kappaB activation, thus allowing HTLV-1-infected cells to proliferate, persist, and evolve |
| 21552325 | Finally, inactivation of the senescence checkpoint can facilitate persistent NF-kappaB activation and leukemogenesis |
| 21536657 | CPEB control of NF-kappaB nuclear localization and interleukin-6 production mediates cellular senescence |
| 21536657 | CPEB regulates the production of IL-6 at both the translational and transcriptional levels; in CPEB-depleted cells, aberrant IL-6 transcription is mediated by improper NF-kappaB p65 phosphorylation and nuclear localization |
| 21471201 | SIRT1 phosphorylation caused concomitant increases in p65/RelA NF-kappaB acetylation and the expression of an anti-apoptotic Bfl-1/A1 |
| 21399611 | Mechanistically, p38MAPK induced the SASP largely by increasing NF-kappaB transcriptional activity |
| 21334198 | Furthermore, combined treatment with nutlin-3 and an inhibitor of NF-kappaB produced synergistic antineoplastic activity in ES cells |
| 21242976 | Moreover 65 of the up and 26 of the downregulated genes are known downstream targets of nuclear factor (NF)-kappaB suggesting that senescence was associated with activation of the NF-kappaB pathway |
| 21242976 | Direct perturbation of this pathway bypasses growth arrest indicating that activation of NF-kappaB signalling has a causal role in promoting senescence |
| 21212468 | Zfra (zinc finger-like protein that regulates apoptosis) is a naturally occurring short peptide consisting of 31 amino acids, which regulates tumor necrosis factor (TNF)-mediated cell death by interacting with receptor adaptor protein TRADD (TNF receptorassociated death domain protein) and downstream JNK (c-Jun N-terminal kinase), NF-kappaB (Nuclear factor kappa B) and WWOX/WOX1 (WW domain-containing oxidoreductase) |
| 21106948 | Reporter and chromatin immunoprecipitation assays identified a previously unrecognized nuclear factor-kappaB (NF-kappaB) response element in the TERT promoter, to which NF-kappaB is recruited during inflammation |
| 21106948 | Inhibition of NF-kappaB signaling completely abolished the induction of TERT expression, characterizing TERT as a bona fide NF-kappaB target gene |
| 21106948 | CONCLUSIONS: These results characterize TERT as a previously unrecognized NF-kappaB target gene in macrophages and demonstrate that telomerase is activated during atherosclerosis |
| 20940041 | Control of p53 and NF-kappaB signaling by WIP1 and MIF: role in cellular senescence and organismal aging |
| 20940041 | The stress-activated signaling pathways, p53 and NF-kappaB, have a major role in the regulation of cellular senescence and organismal aging |
| 20940041 | WIP1 (wildtype p53-induced phosphatase 1) and MIF (macrophage migration inhibitory factor) are signaling molecules which link together the p53 and NF-kappaB pathways via positive and negative feedback loops |
| 20940041 | It seems that the efficiency of the p53 signaling pathway declines during aging whereas that of NF-kappaB is clearly enhanced |
| 20940041 | Moreover, p53 is an important trigger of cellular senescence while NF-kappaB signaling seems to be involved in the induction of the senescence-associated secretory phenotype (SASP) |
| 20940041 | MIF is a pro-inflammatory cytokine which inhibits the function of p53 signaling whereas it is linked to NF-kappaB signaling via a positive feedback loop |
| 20940041 | An increased level of MIF can support inflammatory responses via enhancing NF-kappaB signaling and repressing the function of p53 |
| 20940041 | Decreased WIP1 activity potentiates the activity of p38MAPK and NF-kappaB signaling leading to premature cellular senescence as well as low-level chronic inflammation |
| 20940041 | We will review the findings linking WIP1 and MIF to specific signaling responses of p53 and NF-kappaB and discuss their role in the regulation of cellular senescence and organismal aging |
| 20937593 | Curcumin enhances the effect of cisplatin in suppression of head and neck squamous cell carcinoma via inhibition of IKKbeta protein of the NFkappaB pathway |
| 20937593 | Chromatin immunoprecipitation assay on DNA isolated from IKKbeta immunoprecipitated samples showed PCR amplification of interleukin-8 promoter sequences, a binding site of NFkappaB, indicating an interaction between IKKbeta and NFkappaB |
| 20937593 | Curcumin inhibited IKKbeta in the cytoplasm and nucleus, leading to reduced NFkappaB activity, with no effect on phospho-AKT |
| 20937593 | The suppressive effect of curcumin was mediated through inhibition of cytoplasmic and nuclear IKKbeta, resulting in inhibition of NFkappaB activity |
| 20692358 | HDAC inhibitor-induced activation of NF-kappaB prevents apoptotic response of E1A+Ras-transformed cells to proapoptotic stimuli |
| 20692358 | HDACI-dependent activation of NF-kappaB prevents the induction of apoptosis by cytostatic agent adriamycin and serum deprivation |
| 20692358 | Accordingly, suppression of NF-kappaB activity in HDACI-arrested cells by the chemical inhibitor CAPE or RelA-siRNA resulted in the induction of an apoptotic programme |
| 20692358 | Thus, our findings suggest that the activation of the NF-kappaB pathway in HDACI-treated E1A+Ras-transformed cells blocks apoptosis and may thereby play a role in triggering the programme of cell cycle arrest and cellular senescence |
| 20627123 | For example, sumoylation modulates multiple components in the NFkappaB pathway and exerts an anti-inflammatory effect |
| 20525429 | In summary, hUCMSCs exhibiting senescence are detrimental to cell engraftment and differentiation in animal models via activation of NF-kappaB pathway |
| 20450879 | Naturally occurring dietary polyphenols, such as resveratrol, curcumin, quercetin, and catechins, have antioxidant and anti-inflammatory properties via modulating different pathways, such as NF-kappaB- and mitogen activated protein kinase-dependent signaling pathways |
| 20354187 | JNK2 prevents Ras-induced cell senescence and growth arrest by reducing the expression levels of the cell cycle inhibitor p16 and the activation of NF-kappaB |
| 20016203 | Senescence of cultured porcine coronary arterial endothelial cells is associated with accelerated oxidative stress and activation of NFkB |
| 20016203 | The basal and stimulated (by TNF-alpha) levels of NFkappaB were augmented in senescent cells in electrophoretic mobility shift assays in association with increased oxidative stress, increased p53 protein stability, and activated apoptotic pathways |
| 20016203 | CONCLUSIONS: After multiple passaging in vitro, porcine coronary endothelial cells exhibited dysfunction and senescence associated with reduced proliferative capacity, increased oxidative stress, and activation of the NFkappaB and p53 signaling pathways |
| 20016134 | METHODS: We exposed alveolar type II-like epithelial (A549) cells to a G-quadruplex-interacting telomerase inhibitor in vitro to induce cellular senescence and analyzed the production of proinflammatory cytokines and the activation of NF-kappaB |
| 20016134 | RESULTS: Senescent A549 cells and HDMECs, whether stimulated with lipopolysaccharide or not, produced greater amounts of IL-6, IL-8 and TNF-alpha, which paralleled NF-kappaB activation, than did presenescent cells |
| 20016134 | There were positive correlations between the percentages of senescent type II cells that expressed p16(INK4a) and the percentages of type II cells that expressed phosphorylated NF-kappaB |
| 20016134 | Higher percentages of p16(INK4a)-positive senescent type II cells than of p16(INK4a)-negative presenescent type II cells were positive for phosphorylated NF-kappaB |
| 19805069 | Furthermore, IL-1alpha depletion reduced the DNA binding activity of NF-kappaB and C/EBPbeta, which stimulate IL-6/IL-8 transcription |
| 19779484 | Nuclear factor (NF)-kappaB is a positive regulator of tumour development and progression, but how it functions in normal cells leading to oncogenesis is not clear |
| 19779484 | As cellular senescence has proven to be an intrinsic tumour suppressor mechanism that cells must overcome to establish deregulated growth, we used primary fibroblasts to follow NF-kappaB function in cells transitioning from senescence to subsequent immortalization |
| 19779484 | Significantly, these results can also be duplicated in human fibroblasts lacking NF-kappaB |
| 19779484 | Altogether, our findings present a fresh perspective on the role of NF-kappaB as a tumour suppressor, which acts in pre-neoplastic cells to maintain cellular senescence by promoting DNA repair and genomic stability |
| 19174186 | Atypical pathways of NF-kappaB activation and aging |
| 19174186 | The eukaryotic transcription factor Nuclear Factor-kappaB (NF-kappaB) is a master regulator for inflammatory responses, mediating cellular defense against infectious agents and environmental and cellular stress |
| 19174186 | However, recent evidence-based studies have demonstrated that constitutive activation of NF-kappaB is a ubiquitous phenomenon among various cell types in the aging phenotype, contributing deleterious effects that oppose the acutely beneficial effects of NF-kappaB seen in the inflammatory response |
| 19174186 | Expression of NF-kappaB with age is consistent with elevated levels of inflammatory markers and a pro-inflammatory phenotype, manifested in many age-associated diseases |
| 19174186 | While inducible activating mechanisms for NF-kappaB in the innate immune response are well characterized, constitutive activation in aging cells warrants further investigation of mechanisms collectively called atypical pathways |
| 19174186 | In this review, we provide a comprehensive examination of such NF-kappaB activating mechanisms, including mitochondrial dysfunction, endoplasmic stress response, organelle cross-talk, secondary messengers and DNA damage |
| 19174186 | Investigation of mechanisms of NF-kappaB in aging as an important marker of cellular stress provides guidance for the development of a systems view of cellular aging |
| 19135889 | Here we show that SIRT6 functions at chromatin to attenuate NF-kappaB signaling |
| 19135889 | SIRT6 interacts with the NF-kappaB RELA subunit and deacetylates histone H3 lysine 9 (H3K9) at NF-kappaB target gene promoters |
| 19135889 | We propose that SIRT6 attenuates NF-kappaB signaling via H3K9 deacetylation at chromatin, and hyperactive NF-kappaB signaling may contribute to premature and normal aging |
| 18957176 | TIG-1 cells under the condition of SIPS caused by sublethal and chronic low doses of H2O2 showed nuclear factor-kappaB (NF-kappaB) translocation to the nucleus from the cytosol, while Kangen-karyu extract inhibited NF-kappaB nuclear translocation, implying that Kangen-karyu extract could exert an anti-aging effect through NF-kappaB modulation |
| 18848576 | The senescence-regulating effect of selective COX-2 inhibitors had no correlation with cellular reactive oxygen species levels, NF-kappaB activities or protein levels of p53 and p21 |
| 18603122 | NF-kappaB as a determinant of distinct cell death pathways |
| 18555777 | Cells undergoing OIS secrete multiple CXCR2-binding chemokines in a program that is regulated by the NF-kappaB and C/EBPbeta transcription factors and coordinately induce CXCR2 expression |
| 18362329 | This coincides with up-regulation of p53 and dysregulation of NF-kappaB |
| 18239191 | The mechanism underlying this finding was associated with decreased NF-kappaB activation, and reactive oxygen species generation by decreased phosphorylation of p47(phox) and down-modulating the activation of p21-activated kinase |
| 17142862 | The upregulation of the transcription factor nuclear factor kappaB (NF-kappaB) in transformed hepatocytes, through the paracrine action of tumor necrosis factor-alpha from neighboring endothelia and inflammatory cells, may be critical for tumor progression given the mitogenic and anti-apoptotic properties of proteins encoded by many of NF-kappaB's target genes |
| 17050172 | In contrast, no changes in SA-beta-Gal-positive cell formation were detected by NFkappaB inhibitor, N-alpha-tosyl-L-phenylalanyl chloromethyl ketone (TPCK) |
| 16798746 | Moreover, cotreatment with an IkappaBalpha phosphorylation inhibitor, BAY-11-7082, or a specific NFkappaB nuclear translocation inhibitor, SN50, significantly attenuated the raloxifene-induced telomerase activity and the association of NFkappaB with hTERT |
| 16798746 | These results show that raloxifene induced the up-regulation of telomerase activity not only by the transcriptional regulation of hTERT but also by post-translational regulation of the phosphorylation of Akt and hTERT and the association of hTERT with NFkappaB in HUVECs |
| 16300653 | Up-regulation of the transcription factor NF-kappaB in transformed hepatocytes, through the paracrine action of TNF-alpha from neighbouring endothelia and inflammatory cells, may be critical for tumour progression given the mitogenic and antiapoptotic properties of proteins encoded by many of NF-kappaB's target genes |
| 16259763 | The observation that Kangen-karyu extract prevented nuclear factor kappa B (NF-kappaB) translocation in response to oxidative stress suggested that Kangen-karyu exerted its anti-aging effect through NF-kappaB modulation and prevention of H(2)O(2)-induced overexpression of haem oxygenase-1 protein |
| 15978720 | Cellular damage by oxygen free radicals is a primary driving force for aging and increased activation of redox-regulated transcription factors, such as NF-kappaB that regulate the expression of pro-inflammatory molecules, has been documented in aged animals/individuals versus their young counterparts |
| 15711569 | Here, we present evidence from both cell systems to support a p53-mediated ICAM-1 overexpression in senescent cells that is independent of NF-kappaB |
| 15663361 | And, finally, we show that there is no change in NF-kappaB or Blimp-1 in old vs young stimulated B cells |
| 15572682 | They include mouse Tid1, a homologue of the Drosophila tumor suppressor gene l(2)tid, recently implicated in modulation of apoptosis as well as gamma interferon and NF-kappaB signaling |
| 15572682 | Modulation of endogenous Tid1 activity by GSE-Tid1 or Tid1-specific RNA interference alleviates the suppression of tumor necrosis factor alpha-induced NF-kappaB activity by Tid1 |
| 15572682 | We also show that NF-kappaB sequence-specific binding is strongly downregulated upon senescence in rat embryo fibroblasts |
| 15572682 | We therefore propose that Tid1 contributes to senescence by acting as a repressor of NF-kappaB signaling |
| 15492272 | We now document that overexpression of hPNPase(old-35) results in increased production of ROS, leading to activation of the nuclear factor (NF)-kappaB pathway |
| 15492272 | The generation of ROS and activation of NF-kappaB by hPNPase(old-35) are prevented by treatment with a cell-permeable antioxidant, N-acetyl-l-cysteine |
| 15492272 | We hypothesize that hPNPase(old-35) might play a significant role in producing pathological changes associated with aging by generating proinflammatory cytokines via ROS and NF-kappaB |
| 15247038 | Although the role of the nuclear factor-kappa B (NF-kappa B) signaling cascade is crucial in ICAM-1 activation, we have shown that p53 directly activates the expression of ICAM-1 in an NF-kappa B-independent manner |
| 15064751 | Many of the downstream events of LMP1 expression are mediated through its ability to activate NF-kappaB |
| 12473065 | In addition, it may be possible to utilize these Apo2L/TRAIL preparations for the treatment of various sun-induced skin cancers as they can differentially trigger apoptosis of transformed keratinocytes, or keratinocytes with abnormal NF-kappaB signaling, while sparing adjacent normal keratinocytes |
| 10094826 | Attenuation of NF-kappaB signaling response to UVB light during cellular senescence |
| 10094826 | The aim of this study was to find out whether replicative senescence affects the response of the NF-kappaB signaling pathway to UVB light in human WI-38 and IMR-90 fibroblasts |
| 10094826 | UVB exposure induced a prominent activation of the NF-kappaB signaling pathway both in early and in late passage WI-38 and IMR-90 fibroblasts |
| 10094826 | This attenuation was most prominent in DNA binding activities of nuclear NF-kappaB complexes |
| 10094826 | Transient transfection assays with TK5-CAT and TK10-CAT plasmids carrying NF-kappaB-responsive sites of the TNFalpha promoter were used to analyze the functional activity of the NF-kappaB complexes |
| 9781837 | As a reference, we measured the binding activity to NFkB sequence |
| 9680181 | Redox signals and NF-kappaB activation in T cells |
| 9680181 | Accumulating data from a number of laboratories have recently indicated that the response of transcription factor NF-kappaB to alterations in the redox homeostasis of cells may play an important role in modulating immune function |
| 9680181 | The activation of NF-kappaB has been recognized to regulate a number of genes necessary for normal T cell responses including IL-2, IL-6, IL-8, and several T cell surface receptors |
| 9680181 | Diminished NF-kappaB activity has been shown to occur in T cells with aging, suggesting that impaired activation of NF-kappaB might occur during cellular senescence |
| 9680181 | In addition, aberrancies in NF-kappaB activity have been implicated in the immunopathogenesis of diseases involving immune or inflammatory processes such as atherosclerosis and HIV-1 infection |
| 9680181 | The role of H2O2 and other reactive oxygen species (ROS) as an integratory secondary messenger for divergent T cell signals has been complicated by the fact that various T cell lines and peripheral blood T cells differ markedly in the levels of NF-kappaB activation induced by oxidant stress |
| 9680181 | Additionally, proposed pathways of NF-kappaB activation have been based on indirect evidence provided by experiments which used antioxidants to inhibit active NF-kappaB formation |
| 9680181 | Similarly, substantial evidence indicates that full activation of NF-kappaB requires dual signals |
| 9680181 | The ability of H2O2 or other ROS to induce T cell signals and functional responses by these two mechanisms is reviewed and the specific response of NF-kappaB to redox changes in T cells is examined |
| 9680181 | Data are also presented to suggest that the redox regulation in NF-kappaB activation may be relevant to immune-related diseases and to aging |
| 8809053 | Transfection assays with NF-kappa B-enhancer-driven chloramphenicol acetyltransferase reporter gene showed a significant down-regulation of NF-kappa B promoter activity in senescent WI-38 fibroblasts |
| 8809053 | In tissues, aging seems to involve specific changes in the regulation of NF-kappa B components and perhaps also changes in the DNA-binding affinities of the NF-kappa B complex |
| 7737374 | Diminished responsiveness of senescent normal human fibroblasts to TNF-dependent proliferation and interleukin production is not due to its effect on the receptors or on the activation of a nuclear factor NF-kappa B |
| 7737374 | TNF induced the activation of a nuclear transcriptional factor, NF-kappa B, equally in both young and senescent cells, which indicates the lack of a defect in the early events of TNF signal transduction in senescent fibroblasts |
| 7737374 | Overall, our results indicate that there is an age-dependent decline in TNF-induced proliferation and in the production of interleukins by fibroblasts; this unresponsiveness appears not to be due to TNF receptors or NF-kappa B activation |
| 7862174 | The action of the other ROS on gene activation will then be reviewed by first looking at their possible involvement in the activation of transcription factors like NF-kappa B |
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