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Dissection of DIAP1 functional domains via a mutant replacement strategy
被引:35
作者:

Yokokura, T
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Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA

Dresnek, D
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Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA

Huseinovic, N
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h-index: 0
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Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA

Lisi, S
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h-index: 0
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Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA

Abdelwahid, E
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h-index: 0
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Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA

Bangs, P
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Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA

White, K
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h-index: 0
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Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA
机构:
[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA
关键词:
D O I:
10.1074/jbc.M409691200
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:
Inhibitor of apoptosis proteins (IAPs) act as endogenous inhibitors of active caspases. Drosophila IAP1 (DIAP1) activity is required to keep cells from undergoing apoptosis. The central cell death regulators Reaper and Hid induce apoptosis very rapidly by inhibiting DIAP1 function. We have developed a system for replacing endogenous DIAP1 with mutant forms of the protein, allowing us to examine the roles of various domains of the protein in living and dying cells. We found that DIAP1 is cleaved by a caspase early after the initiation of apoptosis. This cleavage is required for DIAP1 degradation, but Rpr and Hid can still initiate apoptosis in the absence of cleavage. The cleavage of DIAP1 promotes DIAP1 degradation in a manner dependent on the function of the ubiquitin ligase function of the DIAP1 ring domain. This ring domain function is required for Hid-induced apoptosis. We propose a model that synthesizes our data with those of other laboratories and provide a consistent model for DIAP1 function in living and dying cells.
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页码:52603 / 52612
页数:10
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Berman, B
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Frise, E
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Gibson, M
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机构: Harvard Univ, Biol Labs, FlyBase, Cambridge, MA 02138 USA

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机构: Harvard Univ, Biol Labs, FlyBase, Cambridge, MA 02138 USA

Kaminker, J
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机构: Harvard Univ, Biol Labs, FlyBase, Cambridge, MA 02138 USA

Lewis, S
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机构: Harvard Univ, Biol Labs, FlyBase, Cambridge, MA 02138 USA

Marshall, B
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Misra, S
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机构: Harvard Univ, Biol Labs, FlyBase, Cambridge, MA 02138 USA

Mungall, C
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机构: Harvard Univ, Biol Labs, FlyBase, Cambridge, MA 02138 USA

Prochnik, S
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机构: Harvard Univ, Biol Labs, FlyBase, Cambridge, MA 02138 USA

Richter, J
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机构: Harvard Univ, Biol Labs, FlyBase, Cambridge, MA 02138 USA

Smith, C
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机构: Harvard Univ, Biol Labs, FlyBase, Cambridge, MA 02138 USA

Shu, S
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机构: Harvard Univ, Biol Labs, FlyBase, Cambridge, MA 02138 USA

Tupy, J
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Wiel, C
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