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Posttranslational Regulation of Bim by Caspase‐3
Abstract: 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
Abstract: 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
WAKEYAMA, HIDETOSHI (author) / AKIYAMA, TORU (author) / KADONO, YUHO (author) / NAKAMURA, MASAKI (author) / OSHIMA, YASUSHI (author) / NAKAMURA, KOZO (author) / TANAKA, SAKAE (author)
Annals of the New York Academy of Sciences ; 1116 ; 271-280
2007-11-01
10 pages
Article (Journal)
Electronic Resource
English
caspase‐3 , Bim , osteoclasts , degradation
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