The mitochondrial p53 pathway.
p53 is one of the most mutated tumor suppressors in human cancers and as such has been intensively studied for a long time. p53 is a major orchestrator of the cellular response to a broad array of stress types by regulating apoptosis, cell cycle arrest, senescence, DNA repair and genetic stability. For a long time it was thought that these functions of p53 solely rely on its function as a transcription factor, and numerous p53 target genes have been identified [1]. In the last 8 years however, a novel transcription-independent proapoptotic function mediated by the cytoplasmic pool of p53 has been revealed. p53 participates directly in the intrinsic apoptosis pathway by interacting with the multidomain members of the Bcl-2 family to induce mitochondrial outer membrane permeabilization. Our review will discuss these studies, focusing on recent advances in the field.
Vaseva
Angelina V
AV
Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA.
Moll
Ute M
UM
D017209:Apoptosis / Q000235:genetics; D002545:Brain Ischemia / Q000473:pathology; D016923:Cell Death; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D019254:Genes, bcl-2; D006801:Humans; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology; D008928:Mitochondria / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics*; D021381:Protein Transport / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D016159:Tumor Suppressor Protein p53