Letter abstract
Nature Cell Biology 6, 443 - 450 (2004)
Published online: 11 April 2004 | doi:10.1038/ncb1123
Mitochondrial p53 activates Bak and causes disruption of a Bak–Mcl1 complex
J. I-Ju Leu1, Patrick Dumont2, Michael Hafey2, Maureen E. Murphy2 & Donna L. George1
The tumour suppressor activity of the p53 protein has been explained by its ability to induce apoptosis in response to a variety of cellular stresses1, 2. Thus, understanding the mechanism by which p53 functions in the execution of cell death pathways is of considerable importance in cancer biology. Recent studies have indicated that p53 has a direct signalling role at mitochondria in the induction of apoptosis3, 4, 5, 6, although the mechanisms involved are not completely understood. Here we show that, after cell stress, p53 interacts with the pro-apoptotic mitochondrial membrane protein Bak. Interaction of p53 with Bak causes oligomerization of Bak and release of cytochrome c from mitochondria. Notably, we show that formation of the p53–Bak complex coincides with loss of an interaction between Bak and the anti-apoptotic Bcl2-family member Mcl1. These results are consistent with a model in which p53 and Mcl1 have opposing effects on mitochondrial apoptosis by interacting with, and modulating the activity of, the death effector Bak.
- Department of Genetics, University of Pennsylvania School of Medicine, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
- Department of Pharmacology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Correspondence to: Donna L. George1 e-mail: georged@mail.med.upenn.edu
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