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PUMA couples the nuclear and cytoplasmic proapoptotic function of p53.

Authors
  • Chipuk, Jerry E
  • Bouchier-Hayes, Lisa
  • Kuwana, Tomomi
  • Newmeyer, Donald D
  • Green, Douglas R
Type
Published Article
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Publication Date
Sep 09, 2005
Volume
309
Issue
5741
Pages
1732–1735
Identifiers
PMID: 16151013
Source
Medline
License
Unknown

Abstract

The Trp53 tumor suppressor gene product (p53) functions in the nucleus to regulate proapoptotic genes, whereas cytoplasmic p53 directly activates proapoptotic Bcl-2 proteins to permeabilize mitochondria and initiate apoptosis. Here, we demonstrate that a tripartite nexus between Bcl-xL, cytoplasmic p53, and PUMA coordinates these distinct p53 functions. After genotoxic stress, Bcl-xL sequestered cytoplasmic p53. Nuclear p53 caused expression of PUMA, which then displaced p53 from Bcl-xL, allowing p53 to induce mitochondrial permeabilization. Mutant Bcl-xL that bound p53, but not PUMA, rendered cells resistant to p53-induced apoptosis irrespective of PUMA expression. Thus, PUMA couples the nuclear and cytoplasmic proapoptotic functions of p53.

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