Transcription-independent pro-apoptotic functions of p53.
Induction of apoptosis is one of the central activities by which p53 exerts its tumor-suppressing function. Aside from its primary function as a transcription factor, it can promote apoptosis independent of transcription. Recent studies have started to define the mechanisms of non-transcriptional pro-apoptotic p53 activities operating within the intrinsic mitochondria-mediated pathway of apoptosis. So far, two different mechanisms have been described, each of which was assigned to a specific localization of the p53 protein, either in the cytosol or directly at the mitochondria. Although mechanistically different, both transcription-independent modes of apoptosis induction converge, as they both initiate permeabilization of the outer mitochondrial membrane via activation of the pro-apoptotic Bcl-2 family members Bax or Bak.
Moll
Ute M
UM
Department of Pathology, Stony Brook University, Stony Brook, New York 11794, USA.
Wolff
Sonja
S
Speidel
Daniel
D
Deppert
Wolfgang
W
D017209:Apoptosis; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D024101:Mitochondrial Proteins / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53