Stress-induced p53 runs a direct mitochondrial death program: its role in physiologic and pathophysiologic stress responses in vivo.
It is now well established that a fraction of stress-induced wtp53 protein rapidly translocates to mitochondria in immortalized and transformed cells in culture. Mitochondrial p53 interacts with anti-apoptotic proteins of the Bcl 2 family at the outer mitochondrial membrane, resulting in membrane permeabilization, release of death effectors such as cytochrome C and subsequent rapid apoptosis. The significance and relevance of this direct mitochondrial p53 program to the overall p53-mediated stress response in vivo is underlined by a number of recent studies in animals and primary cells. They all support a role for this direct pathway in the physiologic and pathophysiologic response to genotoxic and hypoxic insults and occur precisely in those tissues where p53 plays a critical role in mediating apotpotis rather than cell cycle arrest.
Erster
Susan
S
Department of Pathology Stony Brook University, Stony Brook, New York 11794-8691, USA.
Moll
Ute M
UM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008954:Models, Biological; D009153:Mutagens / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D009153:Mutagens; D016159:Tumor Suppressor Protein p53