HCSGD entry for MDM2
1. General information
| Official gene symbol | MDM2 |
|---|---|
| Entrez ID | 4193 |
| Gene full name | MDM2 oncogene, E3 ubiquitin protein ligase |
| Other gene symbols | ACTFS HDMX hdm2 |
| 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 | IDA IEA | biological_process |
| GO:0002039 | P53 binding | IPI | molecular_function |
| GO:0004842 | Ubiquitin-protein ligase activity | IDA IMP | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005634 | Nucleus | IDA IEA IMP | cellular_component |
| GO:0005654 | Nucleoplasm | IDA TAS | cellular_component |
| GO:0005730 | Nucleolus | IDA | cellular_component |
| GO:0005737 | Cytoplasm | IMP | cellular_component |
| GO:0005829 | Cytosol | TAS | cellular_component |
| GO:0005886 | Plasma membrane | TAS | cellular_component |
| GO:0006461 | Protein complex assembly | IDA | biological_process |
| GO:0006977 | DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest | IMP TAS | biological_process |
| GO:0007089 | Traversing start control point of mitotic cell cycle | IEA | biological_process |
| GO:0007173 | Epidermal growth factor receptor signaling pathway | TAS | biological_process |
| GO:0007268 | Synaptic transmission | TAS | biological_process |
| GO:0008270 | Zinc ion binding | IDA IEA | molecular_function |
| GO:0008284 | Positive regulation of cell proliferation | TAS | biological_process |
| GO:0008543 | Fibroblast growth factor receptor signaling pathway | TAS | biological_process |
| GO:0009743 | Response to carbohydrate | IEA | biological_process |
| GO:0010039 | Response to iron ion | IEA | biological_process |
| GO:0010628 | Positive regulation of gene expression | IEA | biological_process |
| GO:0010955 | Negative regulation of protein processing | IEA | biological_process |
| GO:0016032 | Viral process | IEA | biological_process |
| GO:0016567 | Protein ubiquitination | IDA IEA | biological_process |
| GO:0016604 | Nuclear body | IDA | cellular_component |
| GO:0018205 | Peptidyl-lysine modification | IMP | biological_process |
| GO:0019899 | Enzyme binding | IPI | molecular_function |
| GO:0030666 | Endocytic vesicle membrane | TAS | cellular_component |
| GO:0031625 | Ubiquitin protein ligase binding | IPI | molecular_function |
| GO:0031648 | Protein destabilization | IDA | biological_process |
| GO:0032026 | Response to magnesium ion | IEA | biological_process |
| GO:0032436 | Positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IDA | biological_process |
| GO:0034504 | Protein localization to nucleus | IDA | biological_process |
| GO:0038095 | Fc-epsilon receptor signaling pathway | TAS | biological_process |
| GO:0042176 | Regulation of protein catabolic process | IDA | biological_process |
| GO:0042220 | Response to cocaine | IEA | biological_process |
| GO:0042493 | Response to drug | IEA | biological_process |
| GO:0042787 | Protein ubiquitination involved in ubiquitin-dependent protein catabolic process | IDA | biological_process |
| GO:0042802 | Identical protein binding | IPI | molecular_function |
| GO:0042975 | Peroxisome proliferator activated receptor binding | IEA | molecular_function |
| GO:0043066 | Negative regulation of apoptotic process | IEA | biological_process |
| GO:0043154 | Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process | IEA | biological_process |
| GO:0043234 | Protein complex | IDA | cellular_component |
| GO:0043278 | Response to morphine | IEA | biological_process |
| GO:0043518 | Negative regulation of DNA damage response, signal transduction by p53 class mediator | IDA | biological_process |
| GO:0045087 | Innate immune response | TAS | biological_process |
| GO:0045184 | Establishment of protein localization | IDA | biological_process |
| GO:0045202 | Synapse | IEA | cellular_component |
| GO:0045472 | Response to ether | IEA | biological_process |
| GO:0045892 | Negative regulation of transcription, DNA-templated | IDA | biological_process |
| GO:0045931 | Positive regulation of mitotic cell cycle | IMP | biological_process |
| GO:0046677 | Response to antibiotic | IEP | biological_process |
| GO:0046827 | Positive regulation of protein export from nucleus | IEA | biological_process |
| GO:0048011 | Neurotrophin TRK receptor signaling pathway | TAS | biological_process |
| GO:0048015 | Phosphatidylinositol-mediated signaling | TAS | biological_process |
| GO:0070301 | Cellular response to hydrogen peroxide | IEA | biological_process |
| GO:0071157 | Negative regulation of cell cycle arrest | IDA IEA | biological_process |
| GO:0071229 | Cellular response to acid | IEA | biological_process |
| GO:0071236 | Cellular response to antibiotic | IEA | biological_process |
| GO:0071301 | Cellular response to vitamin B1 | IEA | biological_process |
| GO:0071312 | Cellular response to alkaloid | IEA | biological_process |
| GO:0071375 | Cellular response to peptide hormone stimulus | IEA | biological_process |
| GO:0071391 | Cellular response to estrogen stimulus | IEA | biological_process |
| GO:0071456 | Cellular response to hypoxia | IEP | biological_process |
| GO:0071494 | Cellular response to UV-C | IEA | biological_process |
| GO:0097110 | Scaffold protein binding | IEA | molecular_function |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.0082153186 | 0.9789333042 | 0.2350384783 | 1.0000000000 |
- 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 | 0.6743945659 |
| GSE13712_SHEAR | Up | 0.9850849080 |
| GSE13712_STATIC | Up | 0.8208229571 |
| GSE19018 | Up | 0.1065474372 |
| GSE19899_A1 | Down | -0.0275976484 |
| GSE19899_A2 | Up | 0.3723029444 |
| PubMed_21979375_A1 | Up | 0.0647557851 |
| PubMed_21979375_A2 | Up | 0.4346835245 |
| GSE35957 | Up | 0.2585963688 |
| GSE36640 | Up | 1.1390357585 |
| GSE54402 | Down | -0.2668751387 |
| GSE9593 | Up | 0.3357642766 |
| GSE43922 | Up | 0.1394350662 |
| GSE24585 | Up | 0.5007390618 |
| GSE37065 | Up | 0.4185280726 |
| GSE28863_A1 | Down | -0.3753992298 |
| GSE28863_A2 | Down | -0.1885045713 |
| GSE28863_A3 | Up | 0.2711953018 |
| GSE28863_A4 | Up | 0.0662725241 |
| GSE48662 | Up | 0.6516376131 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
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- Drugs
Name | Drug | Accession number |
|---|---|---|
| Cis-[4,5-Bis-(4-Bromophenyl)-2-(2-Ethoxy-4-Methoxyphenyl)-4,5-Dihydroimidazol-1-Yl]-[4-(2-Hydroxyethyl)Piperazin-1-Yl]Methanone | DB02872 | EXPT01878 |
| Cis-[4,5-Bis-(4-Chlorophenyl)-2-(2-Isopropoxy-4-Methoxyphenyl)-4,5-Dihyd Roimidazol-1-Yl]-Piperazin-1-Yl-Methanone | DB04144 | EXPT01877 |
- MicroRNAs
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-32-5p | MIMAT0000090 | MIRT006631 | Luciferase reporter assay//qRT-PCR//Western blot | Functional MTI | 22431589 |
| hsa-miR-25-3p | MIMAT0000081 | MIRT006632 | Luciferase reporter assay//qRT-PCR//Western blot | Functional MTI | 22431589 |
| hsa-miR-143-3p | MIMAT0000435 | MIRT007256 | Luciferase reporter assay | Functional MTI | 22330136 |
| hsa-miR-145-5p | MIMAT0000437 | MIRT007257 | Luciferase reporter assay | Functional MTI | 22330136 |
| hsa-miR-18b-5p | MIMAT0001412 | MIRT007287 | Luciferase reporter assay | Functional MTI | 23365201 |
| hsa-miR-605-5p | MIMAT0003273 | MIRT016157 | Reporter assay;Western blot | Functional MTI | 21217645 |
| hsa-miR-504-5p | MIMAT0002875 | MIRT016256 | Western blot;qRT-PCR | Non-Functional MTI | 20542001 |
| hsa-miR-26b-5p | MIMAT0000083 | MIRT028860 | Sequencing | Functional MTI (Weak) | 20371350 |
| hsa-miR-484 | MIMAT0002174 | MIRT041992 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-92a-3p | MIMAT0000092 | MIRT049315 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-3929 | MIMAT0018206 | MIRT052891 | 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: 61 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 27183917 | Targeting the Mdm2 oncoprotein by drugs has the potential of re-establishing p53 function and tumor suppression |
| 27183917 | To overcome these limitations, we inhibited Mdm2 and simultaneously a second negative regulator of p53, the phosphatase Wip1/PPM1D |
| 27183917 | Simultaneous inhibition of Mdm2 and Wip1 enhanced cell senescence and G2/M accumulation |
| 27183917 | Taken together, the inhibition of Wip1 might fortify p53-mediated tumor suppression by Mdm2 antagonists |
| 27129219 | HBP1-mediated Regulation of p21 Protein through the Mdm2/p53 and TCF4/EZH2 Pathways and Its Impact on Cell Senescence and Tumorigenesis |
| 27129219 | HBP1-mediated elevation of p21 through the Mdm2/p53 and TCF4/EZH2 pathways contributes to both cellular senescence and tumor inhibition |
| 27016071 | In this setting, it appears that mTORC1 activates senescence through HDM2 phosphorylation, facilitating a p53-mediated response |
| 27016071 | Inhibition of mTORC1 by rapamycin decreases HDM2 phosphorylation and blocks activation of the senescence program in human cells |
| 26915821 | Additionally, we found that ZFP871 physically interacts with p53 and MDM2 proteins |
| 26915821 | Together, we hypothesize that PCBP4 is a potential tissue-specific tumor suppressor and that ZFP871 is part of MDM2 and possibly other ubiquitin E3 ligases that target p53 for degradation |
| 26598601 | The effectiveness of p53 restoration was not dependent on p19(Arf) expression but showed an inverse correlation with Mdm2 expression |
| 26309394 | Moreover, induction of cellular senescence and G0/G1 arrest by 20(S)-Rg3 were accompanied by a large accumulation of p53 and p21 as a result of murine double minute 2 (MDM2) inhibition |
| 26181202 | This is primarily achieved through elevation in the expression of the key inhibitors of p53: Mdm2 or Mdmx (also called Mdm4) (reviewed) |
| 26078718 | Analysis of the mechanism underlying the up-regulation of NQO1 expression during senescence identified that NQO1 promotes p53 accumulation in an MDM2 and ubiquitin independent manner, which reinforces the cellular senescence phenotype |
| 25732822 | Oncogenic stress accelerates rRNA transcription and replicative stress delays rRNA processing, resulting in RPL11 and RPL5 accumulation in the ribosome-free fraction, where they bind MDM2 |
| 25398437 | Mdm2 and aurora kinase a inhibitors synergize to block melanoma growth by driving apoptosis and immune clearance of tumor cells |
| 25398437 | Here, we show how combining a senescence-inducing inhibitor of the mitotic kinase Aurora A (AURKA) with an MDM2 antagonist activates p53 in senescent tumors harboring wild-type 53 |
| 25398437 | Moreover, the prominent response of patient-derived melanoma tumors to coadministered MDM2 and AURKA inhibitors offers a sound rationale for clinical evaluation |
| 25382750 | Furthermore, UBTD1 increased the stability of p53 protein, by promoting the degradation of Mdm2 protein |
| 25382750 | Our results establish UBTD1 as a regulator of cellular senescence that mediates p53 function, and provide insights into the mechanism of Mdm2 inhibition that impacts p53 dynamics during cellular senescence and tumourigenesis |
| 25345926 | It turned out that HOPX inhibited tumour cell proliferation rate, migration, and invasion, and, more interestingly, forced expression of HOPX enhanced cellular senescence via activation of oncogenic Ras and the downstream MAPK pathway, which in turn led to decreased MDM2 and increased p21 |
| 24094550 | METHODS AND RESULTS: To investigate the molecular pathways of replicative cellular senescence, we first evaluated cellular senescence in ex vivo-expanded hCPC(c-kit+) by using senescence-associated beta-galactosidase (SA-beta-gal) activity with enlarged cytoplasm and observed increased expression of cell senescence-related pivotal molecules, including TP53, cleavage Mdm2 (cMdm2), and Mdm2 |
| 24041229 | The interaction between FAK, MYCN, p53 and Mdm2 in neuroblastoma |
| 24041229 | This review focuses on the individual protein tyrosine kinase, focal adhesion kinase (FAK) and its interaction with the transcription factors, MYCN, p53, and Mdm2, and how their interactions modulate the growth and malignancy of neuroblastomas |
| 23952478 | In addition, mouse double minute 2 homolog (MDM2, p53 E3 ubiquitin protein ligase) inhibitor significantly increased the p53 reporter activation in the UVB-irradiated KSC, but morin decreased the MDM2 inhibitor-mediated increase in p53 reporter activation |
| 23952478 | Collectively, these findings suggest that morin could effectively enrich the p53 specific ligasing ability of MDM2 in UVB irradiation-induced p53 activation |
| 23941874 | Mechanistically, we found that diabetes-induced oxidative stress upregulated caveolin-1 (Cav-1) and PTRF expression, which in turn sequestered Mdm2 away from p53 |
| 23766372 | Silencing CK1delta or inhibition of CK1delta activity prevented decay of murine double minute (Mdm)2 |
| 23766372 | Interestingly, a massive increase of p53 in REGgamma(-/-) tissues is associated with reduced Mdm2 protein levels despite that Mdm2 transcription is enhanced |
| 23766372 | Furthermore, introducing exogenous Mdm2 to REGgamma(-/-) MEFs significantly rescues the phenotype of cellular senescence, thereby establishing a REGgamma-CK1-Mdm2-p53 regulatory pathway |
| 23513067 | Nutlins prevent the ubiquitin ligase MDM2 (murine double minute 2), a negative p53 regulator, from interacting with p53 |
| 23513067 | In these mouse models of PH, Nutlin-3a markedly increased senescent p21-stained PA-SMCs; lung p53, p21, and MDM2 protein levels; and p21, Bax, PUMA, BTG2, and MDM2 mRNA levels; but induced only minor changes in control mice without PH |
| 23513067 | Marked MDM2 immunostaining was seen in both mouse and human remodeled pulmonary vessels, supporting the use of Nutlins as a PH-targeted therapy |
| 23478443 | We show that SRSF1 is a necessary component of an MDM2/ribosomal protein complex, separate from the ribosome, that functions in a p53-dependent ribosomal-stress checkpoint pathway |
| 23334421 | Downregulation of ME1 and ME2 reciprocally activates p53 through distinct MDM2- and AMP-activated protein kinase-mediated mechanisms in a feed-forward manner, bolstering this pathway and enhancing p53 activation |
| 23262034 | Molecular pathways: targeting Mdm2 and Mdm4 in cancer therapy |
| 23262034 | In addition, tumor cells dampen p53 activities via overexpression of p53-negative regulators, in particular 2 structurally related proteins, Mdm2 and Mdm4 |
| 23262034 | And yet, Mdm2 and Mdm4 possess p53-independent activities, which also contribute to tumor formation and progression |
| 23262034 | Given that Mdm2 and Mdm4 inhibit p53 activities to promote tumor development, small molecules and peptides were developed to abrogate the inhibition of p53 by Mdm proteins |
| 22783442 | The expression of cyclin D1, Rb, maspin, p53 and mouse double minute 2 (MDM2) was analyzed in 20 paraffin-embedded tissue samples of normal oral mucosa (NOM), 14 samples of oral leukoplakia without dysplasia (OLD-), 11 samples of leukoplakia with dysplasia (OLD+) and 15 samples of oral squamous cell carcinoma (OSCC) by immunohistochemistry in tissue arrays |
| 22783442 | For the ARF-p53 pathway, the expression of p53 and MDM2 was significantly more frequent in the OLD- samples compared to in the NOM ones |
| 22348305 | Bach1-mediated suppression of p53 is inhibited by p19(ARF) independently of MDM2 |
| 22233735 | METHODS: We have analyzed uterine leiomyomas and matching normal tissue for the expression of p14Arf and used explants to see if reducing the MDM2 activity using the small-molecule inhibitor nutlin-3 can induce p53 and activate genes involved in senescence and/or apoptosis |
| 22233735 | In tissue explants, treatment with the MDM2 inhibitor nutlin-3 induced apoptosis as well as senescence as revealed by a dose-dependent increase of the expression of BAX as well as of p21, respectively |
| 22233735 | Because as a rule fibroids express much higher levels of p14Arf, a major negative regulator of MDM2, than matching myometrium it was then analyzed if fibroids are more sensitive against nutlin-3 treatment than matching myometrium |
| 22095030 | In addition, ING proteins are thought to interact with and modulate the function of auxiliary members of p53 pathway, such as MDM2, ARF , p300, and p21, indicating their widespread involvement in the regulation and function of this prominent tumor suppressor pathway |
| 21909130 | We demonstrate that AKT-induced senescence is p53-dependent and is characterised by mTORC1-dependent regulation of p53 translation and stabilisation of p53 protein following nucleolar localisation and inactivation of MDM2 |
| 21718309 | Inactivation of wt-p53 frequently results from dysregulation of MDM2, an E3 ligase that regulates p53 levels |
| 21718309 | Small-molecule drugs that inhibit the interaction of MDM2 and p53 and block p53 degradation are currently tested in clinical trials |
| 21535365 | This senescent phenotype was accompanied by engagement of the p53 tumor suppressor and induction of the p53 target gene p21 and was prevented by small hairpin RNAs against p53, p21, or by the oncoprotein Mdm2 |
| 21498692 | AIM: To address the influence of genes involved in stem cell self-renewal and senescence on the growth of leiomyoma cells in vitro and to explore possible therapeutic implications of a targeted disruption of the p53-murine double minute 2 (MDM2) interaction |
| 21498692 | MATERIALS AND METHODS: Gene expression studies (qRT-PCR) of fibroid tissue and cells; beta-galactosidase stain and qRT-PCR after antagonizing MDM2 |
| 21498692 | Administration of nutlin-3, an MDM2 antagonist, induced cellular senescence and increased the expression of BAX |
| 21498692 | Antagonizing MDM2 induces senescence, as well as apoptosis, and may offer a chance to treat fibroids |
| 21483692 | Recently, nutlins, small-molecule antagonists of MDM2, have been developed to inhibit p53-MDM2 interaction and activate p53 signaling in cancer cells |
| 21483692 | The results provide a basis for the rational use of MDM2 antagonists as a novel treatment option for glioblastoma patients |
| 21464199 | This nucleolar stress response resulted in a sustained elevation of p53 and the p53 target genes, p21 and Mdm2, in cells with wild-type p53 |
| 21456046 | To see if p14(Arf) can repress HMGA2 by a TP53-dependent mechanism, nutlin-3, a known MDM2 antagonist, was used which not only increased the activity of the senescence, associated markers p21 and beta-galactosidase, but also decreased the expression of HMGA2, suggesting that p14(Arf) indeed influences HMGA2 by a p53-dependent mechanism because nutlin-3 stabilizes p53 |
| 21334322 | In this present study, we have generated mice lacking Mdm2 in the epidermis |
| 21334322 | Deletion of Mdm2, the chief negative regulator of p53, induced an aging phenotype in the skin of mice, including thinning of the epidermis, reduced wound healing, and a progressive loss of fur |
| 21334322 | These results reveal that activation of endogenous p53 by ablation of Mdm2 can induce accelerated aging phenotypes in mice |
| 21334198 | The recently developed small-molecule MDM2 inhibitor nutlin-3 restores wild-type p53 function, resulting in the inhibition of cancer cell growth and the induction of apoptosis |
| 21334198 | We found that treatment with nutlin-3 increased p53 level and induced p53 target gene expression (MDM2, p21, PUMA) in ES cells with wild-type p53, but not in ES cells with mutated p53 |
| 20974249 | Its protein stability is regulated by ubiquitination and proteasomal degradation, mainly mediated by Mdm2 |
| 20974153 | Using a stochastic model of the negative feedback circuit involving p53 and its inhibitor Mdm2, we present the different oscillatory dynamics at the single-cell and population-cell levels as described in the experiments, and the resonant nature of the oscillations is captured |
| 20724842 | The Hdm2-antagonist, Nutlin-3a, has been shown to reactivate p53 and induce a quiescent state in various cancer cell lines, similar to the G(1) arrest observed upon RNAi targeting of Hdm2 in MCF7 breast cancer |
| 20659896 | Subsequently, when stress-induced post-translational modifications start to decline, HDM2 becomes effective in targeting p53 for degradation, thus attenuating the p53 response |
| 20500145 | Finally, ursodeoxycholic acid (UDCA), an endogenous bile acid used to treat cholestatic liver diseases, was recently described as a fine modulator of the complex control of p53 by Mdm-2 |
| 20157557 | Reduced transcriptional activity in the p53 pathway of senescent cells revealed by the MDM2 antagonist nutlin-3 |
| 20157557 | Here, we use the small-molecule MDM2 antagonist, nutlin-3a, to selectively activate p53 and probe functionality of the p53 pathway in senescent human fibroblasts, WI-38 |
| 19855165 | Cellular quiescence caused by the Mdm2 inhibitor nutlin-3A |
| 19855165 | In the same cell lines, the Mdm2 inhibitor nutlin-3a induced p53 but, unexpectedly, caused quiescence (reversible arrest) with a small cell morphology |
| 19737973 | Recently developed MDM2 antagonists, the nutlins, are effective p53 activators and potent antitumor agents in cells with functional apoptotic pathways |
| 19737973 | Our results reveal that the MDM2 antagonist can induce a senescence-like state in all tested cell lines, but it is reversible and cells resume proliferation upon drug removal and normalization of p53 control |
| 19710698 | Activation of p53 by Nutlin-3a, an antagonist of MDM2, induces apoptosis and cellular senescence in adult T-cell leukemia cells |
| 19318577 | Caveolin-1 regulates the antagonistic pleiotropic properties of cellular senescence through a novel Mdm2/p53-mediated pathway |
| 19318577 | We show that caveolin-1 is a novel binding protein for Mdm2 |
| 19015633 | F47R-senescent HeLa cells exhibit a sustained expression of p53, hMDM2 and p21(CIP) proteins and a reduced expression of endogenous HPV18 E6 protein |
| 18706112 | Its negative regulator Mdm2 also demonstrates oscillatory behaviour |
| 18706112 | The first model (ARF model) looks at the mechanism of p14ARF which sequesters Mdm2 and leads to stabilisation of p53 |
| 18706112 | The second model (ATM model) examines the mechanism of ATM activation which leads to phosphorylation of both p53 and Mdm2 and increased degradation of Mdm2, which again results in p53 stabilisation |
| 18577387 | We propose a stochastic model of p53 regulation, which is based on two feedback loops: the negative, coupling p53 with its immediate downregulator Mdm2, and the positive, which involves PTEN, PIP3 and Akt |
| 18577387 | The positive feedback destroys the negative coupling between Mdm2 and p53 by sequestering most of Mdm2 in cytoplasm, so it may no longer prime the nuclear p53 for degradation |
| 18451145 | Nutlin-3, an MDM2 inhibitor, activates p53, resulting in several types of cancer cells undergoing apoptosis |
| 17690110 | In addition, we also found that the TWIST-mediated cellular senescence was regulated through its negative effect on p14(ARF) and subsequent suppression of MDM2/p53 and Chk1/2 DNA damage response pathways |
| 17671205 | Induction of p53-dependent senescence by the MDM2 antagonist nutlin-3a in mouse cells of fibroblast origin |
| 17671205 | Nutlin-3a is a recently discovered small-molecule antagonist of the p53-destabilizing protein murine double minute-2 (MDM2) that induces cell cycle arrest and apoptosis in cancer cells with functional p53 |
| 17500067 | In addition to proteasome-mediated degradation, ubiquitination of p53 by Mdm2 acts a key signal for its nuclear export |
| 17500067 | To elucidate the molecular mechanism of degradation-independent repression on p53 by Mdm2, we have developed a two-step approach to purify ubiquitinated forms of p53 induced by Mdm2 from human cells |
| 17500067 | Ubiquitination-mediated repression of p53 by Mdm2 acts at least, in part, through inhibiting the sequence-specific DNA binding activity |
| 17500067 | Thus, our results have important implications regarding the mechanisms by which Mdm2 acts on p53 |
| 17332370 | Instead, depletion of Hsp72 reduced stability and activity of the p53 inhibitor Hdm2 |
| 17297463 | ARF promotes accumulation of retinoblastoma protein through inhibition of MDM2 |
| 17297463 | We have recently shown that MDM2 interacts with Rb and promotes proteasome-dependent Rb degradation |
| 17297463 | Wild-type ARF, but not ARF mutant defective in MDM2 interaction, stabilizes Rb and inhibits colony foci formation independent of p53 |
| 16901784 | These antiproliferative activities are canceled by coexpression of the HDM2 and CDK4 oncogenes, which are often coamplified with HMGA2 in human cancers |
| 16093429 | The purpose of this study was to determine whether MDM2 inhibition enhances the radiosensitivity of a lung cancer model |
| 16093429 | The effects of MDM2 inhibition on tumor vasculature were also studied |
| 16093429 | Transient transfection of H460 lung cancer cells and human umbilical vascular endothelial cells (HUVEC) with antisense oligonucleotides (ASODN) against MDM2 resulted in a reduced level of MDM2 and increased levels of p21 and p53 |
| 16093429 | Clonogenic assays showed that inhibition of MDM2 greatly decreased cell survival following irradiation |
| 16093429 | H460 xenografts that were treated with MDM2 ASODN plus radiotherapy also showed significant growth delay (P < 0 |
| 16093429 | A combination of radiotherapy and inhibition of MDM2 through the antisense approach results in improved tumor control in the H460 lung cancer model |
| 15838523 | There are at least seven negative and three positive feedback loops described here, and of these, six act through the MDM-2 protein to regulate p53 activity |
| 12668979 | Recent data show that cyclin G1 can regulate the levels of p53 by a mechanism that involves dephosphorylation of Mdm2 by protein phosphatase 2A |
| 12668979 | Taken with recent published data, our results suggest that cyclin G1, together with Mdm2, constitute a part of a negative feedback system that attenuates the activity of p53 |
| 11880381 | Microinjection of expression vectors encoding either MDM2 or a pRb-binding mutant of SV40 T antigen, both of which abrogate p53 function, stimulated quiescent normal human fibroblasts to initiate DNA synthesis and were 40-70% as effective as wild-type T antigen |
| 11781307 | Alterations in the MDM2 protein in response to DNER accounted for this p21-mediated cell senescence induction |
| 11781307 | An oncogenic K-Ras 4B mutant significantly increased MDM2 proteins coprecipitated with p53, and suppressed p53 transcriptional activity |
| 11781307 | In turn, DNER exerted its function to decrease MDM2 proteins coprecipitated with p53, followed by the stimulation of p53 activity in the presence of the oncogenic K-Ras 4B mutant |
| 11781307 | In addition, overexpression of wild type ERalpha in NIH3T3 cells resulted in the significant increase in the MDM2 protein level and the resultant suppression of p53 transcriptional activity |
| 11781307 | The data imply that the ERalpha-AP1 pathway activated by oncogenic K-Ras 4B mutant contributes to the NIH3T3 cells' transformation by modulating p53 transcriptional activity through MDM2 |
| 11640890 | Reconstitution of dna synthetic capacity in senescent normal human fibroblasts by expressing cellular factors E2F and Mdm2 |
| 11640890 | Expression by recombinant adenovirus of E2F1, E2F2, E2F3, cyclin E/cdk2, and Mdm2 individually resulted in DNA synthesis in 10-30% of cells |
| 11640890 | However, combination of Mdm2 with E2F or cyclin E/cdk2 resulted in 50 to 75% of cells synthesizing DNA |
| 10629547 | Nuclear p53 protein accumulation was found in 60 per cent of the carcinomas, with significant differences in staining characteristics between the Lauren types in the absence of detectable MDM2 protein ( p< 0 |
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