The complexity of p53 stabilization and activation.
A number of proteins are activated by stress stimuli but none so spectacularly or with the degree of complexity as the tumour suppressor p53 (human p53 gene or protein). Once stabilized, p53 is responsible for the transcriptional activation of a series of proteins involved in cell cycle control, apoptosis and senescence. This protein is present at low levels in resting cells but after exposure to DNA-damaging agents and other stress stimuli it is stabilized and activated by a series of post-translational modifications that free it from MDM2 (mouse double minute 2 but used interchangeably to denote human also), a ubiquination ligase that ubiquitinates it prior to proteasome degradation. The stability of p53 is also influenced by a series of other interacting proteins. In this review, we discuss the post-translational modifications to p53 in response to different stresses and the consequences of these changes.
Lavin
M F
MF
The Queensland Institute of Medical Research, Brisbane, Queensland, Australia. martin.lavin@qimr.edu.au
Gueven
N
N
D000107:Acetylation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D006801:Humans; D009153:Mutagens / Q000633:toxicity; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000528:radiation effects; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
D009153:Mutagens; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D004247:DNA; D051736:Proto-Oncogene Proteins c-mdm2; D011065:Poly(ADP-ribose) Polymerases; D011494:Protein Kinases