Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 281, Issue 19, Pages 13566-13573Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M512467200
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Funding
- Medical Research Council [MC_U132670600] Funding Source: Medline
- MRC [MC_U132670600] Funding Source: UKRI
- Medical Research Council [MC_U132670600] Funding Source: researchfish
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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.
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