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Cell Cycle. 2009 Sep 1;8(17):2692-6. Epub 2009 Sep 2.

PUMA cooperates with direct activator proteins to promote mitochondrial outer membrane permeabilization and apoptosis.

Author information

1
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Abstract

The BCL-2 family of proteins regulates apoptosis by controlling mitochondrial outer membrane permeabilization (MOMP). Within the family there are numerous protein-protein interactions that influence MOMP; however, defining the ultimate signal that commits a cell to apoptosis remains controversial. We chose to examine the function of the BH3-only protein, p53 upregulated modulator of apoptosis (PUMA), to define its contribution to MOMP and cooperation with the direct activator proteins. PUMA is a potent regulator of MOMP and our data suggest that this function is attributed to two distinct mechanisms which both rely on PUMA binding to the anti-apoptotic BCL-2 proteins: de-repression and sensitization. Here we will define these interactions and discuss our experiments that suggest PUMA cooperates with direct activator proteins to efficiently induce MOMP and apoptosis.

PMID:
19652530
PMCID:
PMC3228357
DOI:
10.4161/cc.8.17.9412
[Indexed for MEDLINE]
Free PMC Article
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