The mitochondrial p53 pathway

Biochim Biophys Acta. 2009 May;1787(5):414-20. doi: 10.1016/j.bbabio.2008.10.005. Epub 2008 Oct 25.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Apoptosis / genetics
  • Brain Ischemia / pathology
  • Cell Death
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Genes, bcl-2
  • Humans
  • Kidney Diseases / pathology
  • Kidney Diseases / physiopathology
  • Mitochondria / physiology*
  • Neoplasms / genetics*
  • Protein Transport / physiology
  • Reperfusion Injury / physiopathology
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • Tumor Suppressor Protein p53