Hypoxia Pathway

Preferred Label : Hypoxia Pathway;

NCIt related terms : Hypoxia and p53 in the Cardiovascular system;

Alternative definition : BIOCARTA: Hypoxic stress, like DNA damage, induces p53 protein accumulation and p53-dependent apoptosis in oncogenically transformed cells. Unlike DNA 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 DNA damage, hypoxia fails to induce endogenous downstream p53 effector mRNAs 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 DNA damage-inducible signal that is lacking under hypoxic treatment alone. The phosphatidylinositol 3-OH-kinase-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 DNA damage by abrogating binding of HIF-1 with VHL and p53 with Mdm-2, respectively, leads to stabilization and accumulation of transcriptionally active HIF-1 and p53. At the molecular level, DNA damage induces the interaction of p53 with the transcriptional activator p300 as well as with the transcriptional corepressor mSin3A. In contrast, hypoxia primarily induces an interaction of p53 with mSin3A, but not with p300. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_p53hypoxiaPathway;

Details

Origin ID

C39179;

UMLS CUI

C1512576;

Semantic type(s)
- Physiologic Function [UMLS semantic type]
has_gene_product_element
- Apoptosis Regulator BAX [NCIt concept]
- Casein Kinase I Isoform Alpha [NCIt concept]
- Cellular Tumor Antigen p53 [NCIt concept]
- Cyclin-Dependent Kinase Inhibitor 1 [NCIt concept]
- E3 Ubiquitin-Protein Ligase MDM2 [NCIt concept]
- Four and a Half LIM Domains Protein 2 [NCIt concept]
- Growth Arrest and DNA Damage-Inducible Protein GADD45 Alpha [NCIt concept]
- Heat Shock 70 kDa Protein 1A/1B [NCIt concept]
- Heat Shock Protein HSP 90-Alpha [NCIt concept]
- Histone Acetyltransferase p300 [NCIt concept]
- Hypoxia-Inducible Factor 1-Alpha [NCIt concept]
- Insulin-Like Growth Factor-Binding Protein 3 [NCIt concept]
- Mitogen-Activated Protein Kinase 8 [NCIt concept]
- Multidrug Resistance Protein 1 [NCIt concept]
- NAD(P)H Dehydrogenase [Quinone] 1 [NCIt concept]
- NF-Kappa-B Inhibitor Beta [NCIt concept]
- RAC-Alpha Serine/Threonine Kinase [NCIt concept]
- Serine-Protein Kinase ATM [NCIt concept]
- TATA-Box-Binding Protein [NCIt concept]
pathway_has_gene_element
- ABCB1 wt Allele [NCIt concept]
- AKT1 wt Allele [NCIt concept]
- ATM wt Allele [NCIt concept]
- BAX wt Allele [NCIt concept]
- CDKN1A wt Allele [NCIt concept]
- CSNK1A1 wt Allele [NCIt concept]
- EP300 wt Allele [NCIt concept]
- FHL2 wt Allele [NCIt concept]
- GADD45A wt Allele [NCIt concept]
- HIF1A wt Allele [NCIt concept]
- HSP90AA1 wt Allele [NCIt concept]
- HSPA1A wt Allele [NCIt concept]
- HSPA1B wt Allele [NCIt concept]
- IGFBP3 wt Allele [NCIt concept]
- MAPK8 wt Allele [NCIt concept]
- MDM2 wt Allele [NCIt concept]
- NFKBIB wt Allele [NCIt concept]
- NQO1 wt Allele [NCIt concept]
- TBP wt Allele [NCIt concept]
- TP53 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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