hypoxia and p53 in the cardiovascular system
| PAG Title | hypoxia and p53 in the cardiovascular system |
| PAG ID | WAG001451 |
| Type | P |
| Source Link |  BioCarta |
| Publication Reference | NA |
| PAG Description | Hypoxic stress, like D damage, induces p53 protein accumulation and p53-dependent apoptosis in oncogenically transformed cells. Unlike D damage, hypoxia does not induce p53-dependent cell cycle arrest, suggesting that p53 activity is differentially regulated by these two stresses. Hypoxia induces p53 protein accumulation, but in contrast to D damage, hypoxia fails to induce endogenous downstream p53 effector mRs and proteins, such as p21, Bax, CIP1, WAF1 etc. Hypoxia does not inhibit the induction of p53 target genes by ionizing radiation, indicating that p53-dependent transactivation requires a D damage-inducible sigl that is lacking under hypoxic treatment alone. The phosphatidylinositol 3-OH-kise-Akt pathway inhibits p53-mediated transcription and apoptosis. Mdm2, a ubiquitin ligase for p53, plays a central role in regulation of the stability of p53 and serves as a good substrate for Akt. Mdm-2 targets the p53 tumor suppressor for ubiquitin-dependent degradation by the proteasome, but, in addition, the p53 transcription factor induces Mdm-2, thus, establishing a feedback loop. Hypoxia or D damage by abrogating binding of HIF-1 with VHL and p53 with Mdm-2, respectively, leads to stabilization and accumulation transcriptiolly active HIF-1 and p53. At the molecular level, D damage induces the interaction of p53 with the transcriptiol activator p300 as well as with the transcriptiol corepressor mSin3A. In contrast, hypoxia primarily induces an interaction of p53 with mSin3A, but not with p300. |
| Species | Homo sapiens |
| nCoCo Score | 1,501 |
| Base PAG ID | WAG001451 |
| Human Phenotyte Annotation | |
| Curator | PAGER curation team |
| Curator Contact | PAGER-contact@googlegroups.com |
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