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  • Title: PUMA couples the nuclear and cytoplasmic proapoptotic function of p53.
    Author: Chipuk JE, Bouchier-Hayes L, Kuwana T, Newmeyer DD, Green DR.
    Journal: Science; 2005 Sep 09; 309(5741):1732-5. PubMed ID: 16151013.
    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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