Work

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

Year: 2009

Type: article

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.

Source: Cell Cycle

DOI: 10.4161/cc.8.17.9412

Authors: Jerry E. Chipuk, Douglas R. Green

Institution: St. Jude Children's Research Hospital

Language: English

Topic: Cell death mechanisms and regulation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: American Lebanese Syrian Associated Charities, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases