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p53 is cleaved by caspases generating fragments localizing to mitochondria

Sayan, BS; Sayan, AE; Knight, RA; Melino, G; Cohen, GM

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Authors

AE Sayan

RA Knight

G Melino

GM Cohen



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.

Citation

Sayan, B., Sayan, A., Knight, R., Melino, G., & Cohen, G. (2006). p53 is cleaved by caspases generating fragments localizing to mitochondria. Journal of Biological Chemistry, 281(19), 13566-13573. https://doi.org/10.1074/jbc.M512467200

Journal Article Type Article
Publication Date May 1, 2006
Deposit Date Feb 6, 2023
Publicly Available Date Feb 6, 2023
Journal Journal of Biological Chemistry
Print ISSN 0021-9258
Electronic ISSN 1083-351X
Publisher American Society for Biochemistry and Molecular Biology
Volume 281
Issue 19
Pages 13566-13573
DOI https://doi.org/10.1074/jbc.M512467200
Publisher URL https://doi.org/10.1074/jbc.M512467200

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