Genotoxic and non-genotoxic pathways of p53 induction.
Since the initial concept of p53 as a sensor of DNA-damage, the picture of the role of p53 has widened to include the sensing of much more diverse forms of stress, including hypoxia and constitutive activation of growth-promoting cascades. The pathways by which these processes regulate p53 are partially overlapping, but imply different patterns of post-translational modifications. In this review, we summarize current knowledge on post-translational modifications of p53, and we discuss how hypoxia and oncogene activation stresses may induce p53 independently of DNA damage.
Pluquet
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Group of Molecular Carcinogenesis, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372, Lyon, France.
Hainaut
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P
D017209:Apoptosis; D002453:Cell Cycle; D015687:Cell Hypoxia; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism*; D009687:Nuclear Proteins; D009857:Oncogenes / Q000235:genetics; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D009153:Mutagens; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases