Cell biology: PUMA couples the nuclear and cytoplasmic proapoptotic function of p53

Jerry E. Chipuk, Lisa Bouchier-Hayes, Tomomi Kuwana, Donald D. Newmeyer, Douglas R. Green

Research output: Contribution to journalArticlepeer-review

466 Scopus citations

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.

Original languageEnglish
Pages (from-to)1732-1735
Number of pages4
JournalScience
Volume309
Issue number5741
DOIs
StatePublished - 9 Sep 2005
Externally publishedYes

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