The role of p53 in hypoxia-induced apoptosis.
Hypoxia represents one of the most physiologically relevant stresses, having significant roles in both normal development and malignant progression. Exposure to severe hypoxia leads to the accumulation of p53 which can in turn lead to rapid apoptosis. In contrast to the response to DNA-damaging agents, hypoxia-induced p53 has little or no transcriptional transactivation capabilities and instead seems to function primarily as a transrepressor in order to induce apoptosis.
Hammond
Ester M
EM
Department of Radiation Oncology, Centre for Clinical Sciences Research, Stanford University, Stanford, CA 94303-5152, USA. hammonde@stanford.edu
Giaccia
Amato J
AJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051379:Mice; D009369:Neoplasms / Q000098:blood supply*; D009687:Nuclear Proteins / Q000502:physiology; D010766:Phosphorylation; D012097:Repressor Proteins / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; C497443:Hif1a protein, mouse; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53