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Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis.
Science. 2004 Feb 13; 303(5660):1010-4.Sci

Abstract

The tumor suppressor p53 exerts its anti-neoplastic activity primarily through the induction of apoptosis. We found that cytosolic localization of endogenous wild-type or trans-activation-deficient p53 was necessary and sufficient for apoptosis. p53 directly activated the proapoptotic Bcl-2 protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program. p53 also released both proapoptotic multidomain proteins and BH3-only proteins [Proapoptotic Bcl-2 family proteins that share only the third Bcl-2 homology domain (BH3)] that were sequestered by Bcl-xL. The transcription-independent activation of Bax by p53 occurred with similar kinetics and concentrations to those produced by activated Bid. We propose that when p53 accumulates in the cytosol, it can function analogously to the BH3-only subset of proapoptotic Bcl-2 proteins to activate Bax and trigger apoptosis.

Authors+Show Affiliations

Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14963330

Citation

Chipuk, Jerry E., et al. "Direct Activation of Bax By P53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis." Science (New York, N.Y.), vol. 303, no. 5660, 2004, pp. 1010-4.
Chipuk JE, Kuwana T, Bouchier-Hayes L, et al. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. 2004;303(5660):1010-4.
Chipuk, J. E., Kuwana, T., Bouchier-Hayes, L., Droin, N. M., Newmeyer, D. D., Schuler, M., & Green, D. R. (2004). Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science (New York, N.Y.), 303(5660), 1010-4.
Chipuk JE, et al. Direct Activation of Bax By P53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis. Science. 2004 Feb 13;303(5660):1010-4. PubMed PMID: 14963330.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. AU - Chipuk,Jerry E, AU - Kuwana,Tomomi, AU - Bouchier-Hayes,Lisa, AU - Droin,Nathalie M, AU - Newmeyer,Donald D, AU - Schuler,Martin, AU - Green,Douglas R, PY - 2004/2/14/pubmed PY - 2004/3/3/medline PY - 2004/2/14/entrez SP - 1010 EP - 4 JF - Science (New York, N.Y.) JO - Science VL - 303 IS - 5660 N2 - The tumor suppressor p53 exerts its anti-neoplastic activity primarily through the induction of apoptosis. We found that cytosolic localization of endogenous wild-type or trans-activation-deficient p53 was necessary and sufficient for apoptosis. p53 directly activated the proapoptotic Bcl-2 protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program. p53 also released both proapoptotic multidomain proteins and BH3-only proteins [Proapoptotic Bcl-2 family proteins that share only the third Bcl-2 homology domain (BH3)] that were sequestered by Bcl-xL. The transcription-independent activation of Bax by p53 occurred with similar kinetics and concentrations to those produced by activated Bid. We propose that when p53 accumulates in the cytosol, it can function analogously to the BH3-only subset of proapoptotic Bcl-2 proteins to activate Bax and trigger apoptosis. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/14963330/Direct_activation_of_Bax_by_p53_mediates_mitochondrial_membrane_permeabilization_and_apoptosis_ L2 - https://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=14963330 DB - PRIME DP - Unbound Medicine ER -