Publication Date:
2010-12-04
Description:
Although the proteins BAX and BAK are required for initiation of apoptosis at the mitochondria, how BAX and BAK are activated remains unsettled. We provide in vivo evidence demonstrating an essential role of the proteins BID, BIM, and PUMA in activating BAX and BAK. Bid, Bim, and Puma triple-knockout mice showed the same developmental defects that are associated with deficiency of Bax and Bak, including persistent interdigital webs and imperforate vaginas. Genetic deletion of Bid, Bim, and Puma prevented the homo-oligomerization of BAX and BAK, and thereby cytochrome c-mediated activation of caspases in response to diverse death signals in neurons and T lymphocytes, despite the presence of other BH3-only molecules. Thus, many forms of apoptosis require direct activation of BAX and BAK at the mitochondria by a member of the BID, BIM, or PUMA family of proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163443/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163443/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ren, Decheng -- Tu, Ho-Chou -- Kim, Hyungjin -- Wang, Gary X -- Bean, Gregory R -- Takeuchi, Osamu -- Jeffers, John R -- Zambetti, Gerard P -- Hsieh, James J-D -- Cheng, Emily H-Y -- P30CA21765/CA/NCI NIH HHS/ -- R01 CA125562/CA/NCI NIH HHS/ -- R01 CA125562-02/CA/NCI NIH HHS/ -- R01 CA125562-03/CA/NCI NIH HHS/ -- R01 CA125562-04/CA/NCI NIH HHS/ -- R01CA125562/CA/NCI NIH HHS/ -- R01GM083159/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 3;330(6009):1390-3. doi: 10.1126/science.1190217.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21127253" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Apoptosis
;
Apoptosis Regulatory Proteins/deficiency/genetics/*metabolism
;
BH3 Interacting Domain Death Agonist Protein/deficiency/genetics/*metabolism
;
Caspases/metabolism
;
Cells, Cultured
;
Cerebellum/cytology
;
Cytochromes c/metabolism
;
Intracellular Membranes/metabolism
;
Membrane Proteins/deficiency/genetics/*metabolism
;
Mice
;
Mice, Knockout
;
Mitochondria/metabolism
;
Models, Biological
;
Neurons/*physiology
;
Permeability
;
Protein Multimerization
;
Proto-Oncogene Proteins/deficiency/genetics/*metabolism
;
Stress, Physiological
;
T-Lymphocytes/physiology
;
Tumor Suppressor Proteins/deficiency/genetics/*metabolism
;
bcl-2 Homologous Antagonist-Killer Protein/chemistry/genetics/*metabolism
;
bcl-2-Associated X Protein/chemistry/genetics/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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