Publikationsdatum:
2004-02-14
Beschreibung:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chipuk, Jerry E -- Kuwana, Tomomi -- Bouchier-Hayes, Lisa -- Droin, Nathalie M -- Newmeyer, Donald D -- Schuler, Martin -- Green, Douglas R -- AI40646/AI/NIAID NIH HHS/ -- AI47891/AI/NIAID NIH HHS/ -- GM52735/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 13;303(5660):1010-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14963330" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Animals
;
*Apoptosis
;
BH3 Interacting Domain Death Agonist Protein
;
Carrier Proteins/metabolism
;
Cell Line, Transformed
;
Cell Nucleus/metabolism
;
Cells, Cultured
;
Cytochromes c/metabolism
;
Cytosol/metabolism
;
Gene Expression Regulation
;
Genes, p53
;
HeLa Cells
;
Humans
;
Intracellular Membranes/*physiology
;
Liposomes/metabolism
;
Mice
;
Mitochondria/*physiology
;
Mutation
;
Permeability
;
Protein Conformation
;
Proto-Oncogene Proteins/chemistry/genetics/*metabolism
;
Proto-Oncogene Proteins c-bcl-2/metabolism
;
Recombinant Fusion Proteins/metabolism
;
Tumor Suppressor Protein p53/chemistry/*metabolism
;
Ultraviolet Rays
;
Wheat Germ Agglutinins/pharmacology
;
bcl-2-Associated X Protein
;
bcl-X Protein
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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