p53 is cleaved by caspases generating fragments localizing to mitochondria

Berna S. Sayan, A. Emre Sayan, Richard A. Knight, Gerry Melino, Gerald M. Cohen

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

The p53 tumor suppressor protein exerts most of its anti-tumorigenic activity by transcriptionally activating several pro-apoptotic genes. Accumulating evidence also suggests a transcription-independent function of p53 during apoptosis. It has recently been shown that, when activated, a fraction of p53 translocates to mitochondria, causing cytochrome c release. We now demonstrate a caspase-dependent cleavage of p53 resulting in the generation of four fragments, two of which lack a nuclear localization signal and consequently localize to cytosol. Moreover, these two fragments translocate to mitochondria and induce mitochondrial membrane depolarization in the absence of transcriptional activity. This novel feature of p53 supports the model whereby cytosolic p53 exerts major functions in apoptosis and also suggests the presence of a positive feedback loop in which activated caspases cleave p53 to augment mitochondrial membrane depolarization.

Original languageEnglish
Pages (from-to)13566-13573
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number19
DOIs
Publication statusPublished - May 12 2006

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Mitochondria
Depolarization
Mitochondrial Membranes
Caspases
Apoptosis
Membranes
Tumor Suppressor Protein p53
Nuclear Localization Signals
Transcription
Cytochromes c
Cytosol
Genes
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ASJC Scopus subject areas

  • Biochemistry

Cite this

p53 is cleaved by caspases generating fragments localizing to mitochondria. / Sayan, Berna S.; Sayan, A. Emre; Knight, Richard A.; Melino, Gerry; Cohen, Gerald M.

In: Journal of Biological Chemistry, Vol. 281, No. 19, 12.05.2006, p. 13566-13573.

Research output: Contribution to journalArticle

Sayan, Berna S. ; Sayan, A. Emre ; Knight, Richard A. ; Melino, Gerry ; Cohen, Gerald M. / p53 is cleaved by caspases generating fragments localizing to mitochondria. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 19. pp. 13566-13573.
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