BID-D59A is a potent inducer of apoptosis in primary embryonic fibroblasts

被引:70
作者
Sarig, R
Zaltsman, Y
Marcellus, RC
Flavell, R
Mak, TW
Gross, A [1 ]
机构
[1] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel
[2] Geminx Biotechnol Inc, Montreal, PQ H2W 2M9, Canada
[3] Yale Univ, Sch Med, Howard Hughes Med Inst, Immunol Sect, New Haven, CT 06520 USA
[4] Ontario Canc Inst, Amgen Inst, Div Cellular & Mol Biol, Toronto, ON M5G 2M9, Canada
关键词
D O I
10.1074/jbc.M210296200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The proapoptotic activity of BID seems to solely depend upon its cleavage to truncated tBID. Here we demonstrate that expression of a caspase-8 non-cleavable (nc) BID-D59A mutant or expression of wild type (wt) BID induces apoptosis in Bid -/-, caspase-8 -/-, and wt primary MEFs. Western blot analysis indicated that no cleavage products appeared in cells expressing ncBID. ncBID was as effective as wtBID in inducing cytochrome c release, caspase activation, and apoptosis. ncBID and wtBID (nc/wtBID) were much less effective than tBID in localizing to mitochondria and in inducing cytochrome c release, but only slightly less effective in inducing apoptosis. Studies with Apaf-1- and caspase-9-deficient primary MEFs indicated that both proteins were essential for nc/wtBID and for tBID-induced apoptosis. Most importantly, expression of non-apoptotic levels of either ncBID or wtBID in Bid -/- MEFs induced a similar and significant enhancement in apoptosis in response to a variety of death signals, which was accompanied by enhanced localization of BID to mitochondria and cytochrome c release. Thus, these results implicate full-length BID as an active player in the mitochondria during apoptosis.
引用
收藏
页码:10707 / 10715
页数:9
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