Document Detail

Loss of Bif-1 suppresses Bax/Bak conformational change and mitochondrial apoptosis.
MedLine Citation:
PMID:  16227588     Owner:  NLM     Status:  MEDLINE    
Bif-1, a member of the endophilin B protein family, interacts with Bax and promotes interleukin-3 withdrawal-induced Bax conformational change and apoptosis when overexpressed in FL5.12 cells. Here, we provide evidence that Bif-1 plays a regulatory role in apoptotic activation of not only Bax but also Bak and appears to be involved in suppression of tumorigenesis. Inhibition of endogenous Bif-1 expression in HeLa cells by RNA interference abrogated the conformational change of Bax and Bak, cytochrome c release, and caspase 3 activation induced by various intrinsic death signals. Similar results were obtained in Bif-1 knockout mouse embryonic fibroblasts. While Bif-1 did not directly interact with Bak, it heterodimerized with Bax on mitochondria in intact cells, and this interaction was enhanced by apoptosis induction and preceded the Bax conformational change. Moreover, suppression of Bif-1 expression was associated with an enhanced ability of HeLa cells to form colonies in soft agar and tumors in nude mice. Taken together, these findings support the notion that Bif-1 is an important component of the mitochondrial pathway for apoptosis as a novel Bax/Bak activator, and loss of this proapoptotic molecule may contribute to tumorigenesis.
Yoshinori Takahashi; Mariusz Karbowski; Hirohito Yamaguchi; Aslamuzzaman Kazi; Jie Wu; Saïd M Sebti; Richard J Youle; Hong-Gang Wang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  25     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-10-17     Completed Date:  2005-12-20     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9369-82     Citation Subset:  IM    
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MeSH Terms
Adaptor Proteins, Signal Transducing / genetics,  metabolism*
Apoptosis / physiology*
Caspases / metabolism
Cells, Cultured
Cytochromes c / metabolism
Enzyme Activation
Fibroblasts / physiology
HeLa Cells
Mice, Knockout
Mitochondria / physiology*
Neoplasms, Experimental / genetics
Protein Conformation
RNA, Small Interfering / metabolism
bcl-2 Homologous Antagonist-Killer Protein / metabolism*
bcl-2-Associated X Protein / metabolism*
Grant Support
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/BAK1 protein, human; 0/BAX protein, human; 0/Bak1 protein, mouse; 0/Bax protein, mouse; 0/RNA, Small Interfering; 0/SH3GLB1 protein, human; 0/Sh3glb1 protein, mouse; 0/bcl-2 Homologous Antagonist-Killer Protein; 0/bcl-2-Associated X Protein; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases

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