HCSGD entry for MAPK8
1. General information
| Official gene symbol | MAPK8 |
|---|---|
| Entrez ID | 5599 |
| Gene full name | mitogen-activated protein kinase 8 |
| Other gene symbols | JNK JNK-46 JNK1 JNK1A2 JNK21B1/2 PRKM8 SAPK1 SAPK1c |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0001503 | Ossification | 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:0004674 | Protein serine/threonine kinase activity | IDA | molecular_function |
| GO:0004705 | JUN kinase activity | IDA IEA | molecular_function |
| GO:0004707 | MAP kinase activity | IEA | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005524 | ATP binding | IEA | molecular_function |
| GO:0005634 | Nucleus | IDA IEA | cellular_component |
| GO:0005654 | Nucleoplasm | TAS | cellular_component |
| GO:0005739 | Mitochondrion | IEA | cellular_component |
| GO:0005829 | Cytosol | IEA TAS | cellular_component |
| GO:0006915 | Apoptotic process | TAS | biological_process |
| GO:0006950 | Response to stress | TAS | biological_process |
| GO:0007254 | JNK cascade | IDA TAS | biological_process |
| GO:0007258 | JUN phosphorylation | IDA | biological_process |
| GO:0009411 | Response to UV | IDA | biological_process |
| GO:0010468 | Regulation of gene expression | IEA | biological_process |
| GO:0010628 | Positive regulation of gene expression | IMP | biological_process |
| GO:0018105 | Peptidyl-serine phosphorylation | IDA | biological_process |
| GO:0018107 | Peptidyl-threonine phosphorylation | IDA IEA IMP | biological_process |
| GO:0031063 | Regulation of histone deacetylation | IMP | biological_process |
| GO:0032091 | Negative regulation of protein binding | IDA | biological_process |
| GO:0032880 | Regulation of protein localization | IDA | biological_process |
| 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:0035033 | Histone deacetylase regulator activity | IMP | molecular_function |
| 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:0042826 | Histone deacetylase binding | IPI | molecular_function |
| GO:0043065 | Positive regulation of apoptotic process | TAS | biological_process |
| GO:0043066 | Negative regulation of apoptotic process | IDA | biological_process |
| GO:0045087 | Innate immune response | TAS | biological_process |
| GO:0046686 | Response to cadmium ion | IEA | biological_process |
| GO:0048011 | Neurotrophin TRK receptor signaling pathway | TAS | biological_process |
| GO:0051090 | Regulation of sequence-specific DNA binding transcription factor activity | TAS | biological_process |
| GO:0051403 | Stress-activated MAPK cascade | TAS | biological_process |
| GO:0071260 | Cellular response to mechanical stimulus | IEP | biological_process |
| GO:0090045 | Positive regulation of deacetylase activity | IMP | biological_process |
| GO:0097190 | Apoptotic signaling pathway | TAS | biological_process |
| GO:0097193 | Intrinsic apoptotic signaling pathway | TAS | biological_process |
| GO:1900740 | Positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway | TAS | biological_process |
| GO:2000017 | Positive regulation of determination of dorsal identity | IEA | biological_process |
| GO:2001235 | Positive regulation of apoptotic signaling pathway | IEA | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.9599209870 | 0.1066646062 | 0.9999902473 | 0.6251434202 |
- 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 | Up | 0.0503960185 |
| GSE13712_SHEAR | Down | -0.3394464657 |
| GSE13712_STATIC | Down | -0.0411177419 |
| GSE19018 | Down | -0.2141346872 |
| GSE19899_A1 | Up | 0.0612889888 |
| GSE19899_A2 | Down | -0.2088262996 |
| PubMed_21979375_A1 | Up | 0.0064146128 |
| PubMed_21979375_A2 | Down | -0.2588743564 |
| GSE35957 | Up | 0.0466819933 |
| GSE36640 | Down | -0.4457594615 |
| GSE54402 | Up | 0.1247638779 |
| GSE9593 | Down | -0.1693255375 |
| GSE43922 | Up | 0.0295612408 |
| GSE24585 | Up | 0.0239929409 |
| GSE37065 | Up | 0.0440419811 |
| GSE28863_A1 | Down | -0.2401269655 |
| GSE28863_A2 | Down | -0.6301409861 |
| GSE28863_A3 | Down | -0.5677646961 |
| GSE28863_A4 | Up | 0.0390092607 |
| GSE48662 | Up | 0.1076659339 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
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- Drugs
Name | Drug | Accession number |
|---|---|---|
| 2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One | DB01782 | EXPT00232 |
| 6-CHLORO-9-HYDROXY-1,3-DIMETHYL-1,9-DIHYDRO-4H-PYRAZOLO[3,4-B]QUINOLIN-4-ONE | DB07218 | - |
| 2-({2-[(3-HYDROXYPHENYL)AMINO]PYRIMIDIN-4-YL}AMINO)BENZAMIDE | DB07268 | - |
| N-(4-AMINO-5-CYANO-6-ETHOXYPYRIDIN-2-YL)-2-(4-BROMO-2,5-DIMETHOXYPHENYL)ACETAMIDE | DB07272 | - |
| 5-CYANO-N-(2,5-DIMETHOXYBENZYL)-6-ETHOXYPYRIDINE-2-CARBOXAMIDE | DB07276 | - |
| 2-fluoro-6-{[2-({2-methoxy-4-[(methylsulfonyl)methyl]phenyl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzamide | DB07845 | - |
- MicroRNAs
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-214-3p | MIMAT0000271 | MIRT005427 | GFP reporter assay//Microarray//qRT-PCR//Western blot//Reporter assay;qRT-PCR;Microarray;Other | Functional MTI | 19859982 |
| hsa-miR-421 | MIMAT0003339 | MIRT016104 | Sequencing | Functional MTI (Weak) | 20371350 |
| hsa-miR-421 | MIMAT0003339 | MIRT016104 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-193b-3p | MIMAT0002819 | MIRT016510 | Microarray | Functional MTI (Weak) | 20304954 |
| hsa-miR-125a-5p | MIMAT0000443 | MIRT021289 | Sequencing | Functional MTI (Weak) | 20371350 |
| hsa-miR-140-3p | MIMAT0004597 | MIRT021678 | Sequencing | Functional MTI (Weak) | 20371350 |
| hsa-miR-10a-5p | MIMAT0000253 | MIRT025602 | Sequencing | Functional MTI (Weak) | 20371350 |
| hsa-miR-33a-5p | MIMAT0000091 | MIRT028235 | Sequencing | Functional MTI (Weak) | 20371350 |
| hsa-miR-877-5p | MIMAT0004949 | MIRT037323 | CLASH | Functional MTI (Weak) | 23622248 |
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- mirRecord
No target information from mirRecord
6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 30 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 26793112 | It has been shown that there is a JNK pathway activation after exposure to different stressing factors, including cytokines, growth factors, oxidative stress, unfolded protein response signals or Abeta peptides |
| 26793112 | In addition, activation of JNK has been identified as a key element responsible for the regulation of apoptosis signals and therefore, it is critical for pathological cell death associated with neurodegenerative diseases and, among them, with Alzheimer's disease (AD) |
| 26793112 | In addition, in vitro and in vivo studies have reported alterations of JNK pathways potentially associated with pathogenesis and neuronal death in AD |
| 26793112 | This review aims to explain the rationale behind testing therapies based on inhibition of JNK signaling for AD in terms of current knowledge about the pathophysiology of the disease |
| 26515130 | The UPR resulted in upregulation of ER chaperones including BIP/Grp78, Grp94 and led to an activation of IRE1alpha as evidenced by spliced XBP1 mRNA with IRE1alpha-induced JNK phosphorylation |
| 26051603 | When we evaluated signaling pathways, we found that JNK activation involved in LC3 conversion induced by DHEA |
| 26051603 | CONCLUSION: DHEA prevents LA-induced endothelial senescence by restoring autophagy and autophagic flux through JNK activation |
| 25345385 | Mechanistically, mitochondrial defects in conjunction with Ras cause production of reactive oxygen species, downregulation of CycE activity and activation of p53, which cooperate together to trigger a cell cycle arrest-Jun N-terminal kinase (JNK) feedback loop that amplifies JNK activation, leading to upregulation of the inflammatory cytokine Unpaired |
| 25336054 | Examination of the underlying mechanisms indicated that the effect of tripterine is mediated by the induction of heat shock protein 32 expression and the inhibition of JNK activation |
| 25292174 | Conversely, JNK1 content and phosphorylation increased |
| 25077541 | We demonstrate that miR-17 targets both ADCY5 and IRS1, upregulating the downstream signals MKP7, FoxO3, LC3B, and HIF1alpha, and downregulating mTOR, c-myc, cyclin D1, and JNK |
| 24984152 | Cleaved high molecular weight kininogen stimulates JNK/FOXO4/MnSOD pathway for induction of endothelial progenitor cell senescence |
| 24984152 | METHODS AND RESULTS: Treatment of human EPCs with HKa for 72h stimulated JNK phosphorylation at Thr183/Tyr185, and FOXO4 phosphorylation at Thr451, Concomitantly, upregulated the expression of MnSOD at protein and mRNA levels in a concentration-dependent manner |
| 24984152 | CONCLUSION: These results demonstrate that HKa accelerates the onset of EPC senescence by stimulating JNK/FOXO4/MnSOD pathway, its effect is mediated by the HC |
| 24858180 | Inhibition of ERK and JNK reduces, while that of p38 enhances stress-mediated c-fos expression |
| 24400224 | Recent studies have elucidated roles for NF-kappaB, STAT3 and JNK as possible missing links |
| 24389959 | Furthermore, our data showed that activation of MAPK8/9/10 (mitogen-activated protein kinase 8/9/10/c-Jun N-terminal kinases) was an essential upstream signal for PGG-induced autophagy |
| 23354547 | Of note, lentiviralmediated continuous JARID1B depletion resulted in the loss of epithelial differentiation and suppressed CRC cell growth, which was associated with the induction of phosphorylation by the cJun Nterminal kinase (Jnk/Sapk) and senescenceassociated betagalactosidase activity |
| 23461035 | We believe that JNK 1,2 kinases are required for mTORC1 activation and acquiring the markers of premature senescence, induced by NaBut in the E1A+cHa-Ras transformants |
| 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) |
| 21116678 | At the molecular level, age-related resistance to apoptosis involves (1) functional deficiency in p53 network, (2) increased activity in the NF-kappaB-IAP/JNK axis, and (3) changes in molecular chaperones, microRNAs, and epigenetic regulation |
| 20354187 | The c-Jun NH(2)-terminal kinase (JNK) signaling cascade has been implicated in a wide range of diseases, including cancer |
| 20354187 | It is unclear how different JNK proteins contribute to human cancer |
| 20354187 | Most importantly, JNK2, but not JNK1, is sufficient to couple with oncogenic Ras to transform primary human epidermal cells into malignancy with features of SCC |
| 20354187 | On the other hand, JNK, along with phosphoinositide 3-kinase, is essential for Ras-induced glycolysis, an energy-producing process known to benefit cancer growth |
| 19887452 | Although JNK is activated by ROS, this pathway is not associated with cellular senescence of chondrocytes |
| 18952756 | Western blotting of freshly isolated AEC2 lysates for stress signaling kinases confirmed that the stress-activated protein kinase (SAPK)/c-Jun NH(2)-terminal kinase (JNK) stress response pathway is stimulated in telomerase-null AEC2 even under normoxic conditions |
| 18316603 | We show that redistribution of B23 and p19(ARF) after the exposure to genotoxic stress occurs preferentially when the c-Jun-NH(2)-kinase (JNK) pathway is activated and is inhibited when the JNK pathway is impaired |
| 18316603 | The stress-induced translocation of alternative reading frame (ARF) is JNK dependent and mediated by two activator proteins, c-Jun and JunB |
| 18316603 | Hence, we suggest that c-Jun translocates B23 and ARF from the nucleolus after JNK activation by means of protein interactions |
| 18316603 | In senescent cells, JNK activity and c-Jun levels are reduced concomitantly with ARF nucleolar accumulation, and UV radiation does not cause the translocation of ARF |
| 17762881 | Antagonistic control of cell fates by JNK and p38-MAPK signaling |
| 17762881 | Here we report that JNK and p38-MAPK pathways antagonistically control cellular senescence, oncogenic transformation, and proliferation in primary mouse embryonic fibroblasts (MEFs) |
| 17012840 | Although it is well established that a transient activation of the mitogen-activated protein kinases Erk and Jnk is a crucial step in most growth promoting signaling pathways, it has also been demonstrated that a prolonged activation of these kinases can induce differentiation, cell cycle arrest, and cell senescence |
| 17012840 | We recently found that the expression of the 21-kDa human Vaccinia H1-related (VHR) dual-specific phosphatase fluctuates during cell cycle progression and affects Erk and Jnk activity in a cell cycle-dependent manner |
| 17012840 | In the absence of VHR, the serum-induced activation of Jnk and Erk was further elevated and was required for the G(1)/S and G(2)/M blocks, which were attenuated upon Jnk and Erk inhibition |
| 17012840 | Collectively, VHR provides a long sought layer in the regulation of Jnk and Erk during cell cycle progression thereby contributing to cell cycle arrest, differentiation or senescence |
| 16882877 | However, inhibition of p53 with alpha-PFT or p53 siRNA or JNK with SP600125 (1,9-pyrazoloanthrone) failed to protect WI38 cells from BU-induced senescence |
| 15520191 | Ceramide is known to potently activate a number of stress-regulated enzymes, including the c-Jun NH(2)-terminal kinase (JNK) |
| 15520191 | Although ceramide promotes apoptosis in human lung cancer-derived A549 cells, a role for JNK in this process is unknown |
| 15520191 | Here, we report that ceramide promotes apoptosis in A549 cells by a mechanism involving JNK |
| 15520191 | The JNK inhibitor SP600125 proved effective at protecting cells from the lethal effects of ceramide |
| 15520191 | To understand which JNK-mediated pathway may be involved, a number of JNK target proteins were examined, including the transcription factor, c-Jun, and the apoptotic regulatory proteins Bcl-X(L) and Bim |
| 15520191 | On the other hand, ceramide promoted phosphorylation of Bim and induced translocation of active JNK from the nucleus to the cytoplasm and mitochondrial fraction |
| 15520191 | Ceramide-mediated changes in localization of JNK were consistent with the observed changes in phosphorylation status of c-Jun and Bim |
| 15520191 | These results suggest that JNK may participate in ceramide-induced apoptosis in A549 cells by a mechanism involving Bim |
| 15107616 | The c-Jun N-terminal kinase (JNK/SAPK) signaling cascade controls a spectrum of cellular processes, including cell growth, differentiation, transformation, and apoptosis |
| 15107616 | We further explored other molecules involved in JNK pathway and found that both MKK4, another direct activator of JNK, and c-Jun, a direct substrate of JNK, have similar roles to MKK7 |
| 15039780 | Similarly, loss of c-Jun or expression of a c-JunAA mutant in which the JNK phosphorylation sites were replaced with alanine results in a G2/M cell-cycle block |
| 12676512 | However, the mechanisms how ceramide directly activates enzymes such as JNK and PP2A are still not clear |
| 11480555 | Ceramide activates stress-activated protein kinases like c-jun N-terminal kinase (JNK) and thus affects transcription pathways involving c-jun |
| 10987139 | The SAPK/JNK activation by UV irradiation was reduced in both non-treated senescent cells and the hydrogen peroxide-induced senescent cells, suggesting that a reduced DNA fragmentation by UV-irradiation in the senescent cells is closely related to the decreased SAPK/JNK activity |
| 10982848 | Mitochondrial metabolism of pyruvate is demonstrated to activate the c-Jun N-terminal kinase (JNK) |
| 10982848 | This metabolite-induced rise in cytosolic JNK1 activity is shown to be triggered by increased release of mitochondrial H(2)O(2) |
| 10982848 | We further demonstrate that in turn, the redox-dependent activation of JNK1 feeds back and inhibits the activity of the metabolic enzymes glycogen synthase kinase 3beta and glycogen synthase |
| 8876670 | We found that early-passage cells exhibited a greater degree of JNK activation in response to HS and ultraviolet (UV) C light treatments than did late-passage cells |
| 8876670 | Decreased JNK activation was dependent on the number of passages but was not affected by varying doses of UV irradiation |
| 8876670 | A further understanding of this impaired activation of JNK may provide insights into the mechanisms of stress response and cellular aging |
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