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

Jerry E. Chipuk, Douglas R. Green

Research output: Contribution to journalReview articlepeer-review

91 Scopus citations

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 antiapoptotic 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.

Original languageEnglish
Pages (from-to)2692-2696
Number of pages5
JournalCell Cycle
Volume8
Issue number17
DOIs
StatePublished - 1 Sep 2009
Externally publishedYes

Keywords

  • Apoptosis
  • BCL-2 family
  • Cytochrome c release
  • MOMP and PUMA

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