DOI: 10.1126/science.1114297. PUMA Couples the Nuclear and Cytoplasmic Proapoptotic Function of p53

PUMA Couples the Nuclear and Cytoplasmic Proapoptotic Function of p53

10.1126/science.1114297

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

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.

Bibliography

Chipuk, J. E., Bouchier-Hayes, L., Kuwana, T., Newmeyer, D. D., & Green, D. R. (2005). PUMA Couples the Nuclear and Cytoplasmic Proapoptotic Function of p53. Science, 309(5741), 1732â1735.

Authors 5

Jerry E. Chipuk (first)
Lisa Bouchier-Hayes (additional)
Tomomi Kuwana (additional)
Donald D. Newmeyer (additional)
Douglas R. Green (additional)

References 28 Referenced 438

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We thank P. Juin J. Claude Martinou K. Roth A. Strasser B. Sullivan A. Villunger B. Vogelstein K. Vousden and G. Wahl for their generosity with reagents and expertise. This work was supported by grants from the Leukemia and Lymphoma Society (D.R.G.) and the National Institutes of Heath (D.R.G. and D.D.N.). J.E.C. is supported by an Individual National Research Service Award.

Dates

Type	When
Created	19 years, 11 months ago (Sept. 8, 2005, 5:28 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 9:58 p.m.)
Indexed	2 weeks ago (Aug. 7, 2025, 4:54 p.m.)
Issued	19 years, 11 months ago (Sept. 9, 2005)
Published	19 years, 11 months ago (Sept. 9, 2005)
Published Print	19 years, 11 months ago (Sept. 9, 2005)

Funders 0

None

BibTeX

@article{Chipuk_2005, title={PUMA Couples the Nuclear and Cytoplasmic Proapoptotic Function of p53}, volume={309}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1114297}, DOI={10.1126/science.1114297}, number={5741}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Chipuk, Jerry E. and Bouchier-Hayes, Lisa and Kuwana, Tomomi and Newmeyer, Donald D. and Green, Douglas R.}, year={2005}, month=sep, pages={1732–1735} }

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