Posttranslational regulation of bim by caspase-3.

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Posttranslational regulation of bim by caspase-3. Abstract Text:

Hidetoshi Wakeyama,Toru Akiyama,Yuho Kadono,Masaki Nakamura,Yasushi Oshima,Kozo Nakamura,Sakae Tanaka,Hidetoshi Wakeyama,Toru Akiyama,Yuho Kadono,Masaki Nakamura,Yasushi Oshima,Kozo Nakamura,Sakae Tanaka,Hidetoshi Wakeyama,Toru Akiyama,Yuho Kadono,Masaki Nakamura,Yasushi Oshima,Kozo Nakamura,Sakae Tanaka,

Bim is a proapoptotic BH3-domain-only member of the Bcl-2 family, and its expression is regulated both transcriptionally and posttranslationally. We developed an in vitro system examining the posttranslational regulation of Bim. Since Bim is a strong mediator of apoptosis, it has been quite difficult to establish cell lines stably overexpressing Bim. Coexpression of Bcl-2 enabled us to obtain mouse embryonic fibroblasts (MEFs) in which Bim is overexpressed and Bcl-2 expression is regulated by Tet-off system. Reduction of Bcl-2 levels by doxycycline treatment induced caspase-3 and caspase-7 activation, which was followed by Bim degradation. Bim degradation was suppressed by gene knockdown of caspase-3, but not by caspase-7 knockdown. The same posttranslational regulation of Bim was observed in osteoclasts. These results suggest that caspase-3 negatively regulates Bim expression by stimulating its degradation, thus creating a negative feedback loop in the Bim-caspase axis.

Posttranslational regulation of bim by caspase-3. Publishing Authors By Initials

H Wakeyama,T Akiyama,Y Kadono,M Nakamura,Y Oshima,K Nakamura,S Tanaka,H Wakeyama,T Akiyama,Y Kadono,M Nakamura,Y Oshima,K Nakamura,S Tanaka,H Wakeyama,T Akiyama,Y Kadono,M Nakamura,Y Oshima,K Nakamura,S Tanaka,

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Posttranslational regulation of bim by caspase-3. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Annals of the New York Academy of Sciences

VOLUME: 1116

Page Numbers: 271-80

Journal Abbreviation: Ann. N. Y. Acad. Sci.

ISSN: 0077-8923

DAY: 21

MONTH: 06

YEAR: 2007

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LANGUAGE: eng

NlmUniqueID: 7506858

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AFFILIATION: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. TANAKAS-ORT@h.u-tokyo.ac.jp.

Country: United States

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MEDLINETA: Ann N Y Acad Sci

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