An IAP-IAP complex inhibits apoptosis

An IAP-IAP complex inhibits apoptosis
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DOI:
10.1074/jbc.c400236200
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发表时间:
2004-08-13
影响因子:
4.8
通讯作者:
Altieri, DC
Altieri, DC
中科院分区:
生物学2区
文献类型:
--
作者:
Dohi, T;Okada, K;Altieri, DC

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细胞凋亡的调节因子被认为是协同工作的,但这一过程的分子相互作用尚不清楚。在这里,我们表明,在响应细胞死亡刺激,生存素,凋亡抑制因子(IAP)基因家族的成员,与另一个IAP蛋白,XIAP,通过保守的杆状病毒IAP重复。生存素-XIAP复合物的形成促进了XIAP稳定性的增加,以对抗泛素化/蛋白酶体破坏和细胞凋亡的协同抑制,这在XIAP(-/-)细胞中被消除。因此,IAP-IAP复合物的协调调节细胞凋亡。
Regulators of apoptosis are thought to work in concert, but the molecular interactions of this process are not understood. Here, we show that in response to cell death stimulation, survivin, a member of the inhibitor of apoptosis (IAP) gene family, associates with another IAP protein, XIAP, via conserved baculovirus IAP repeats. Formation of a survivin-XIAP complex promotes increased XIAP stability against ubiquitination/proteasomal destruction and synergistic inhibition of apoptosis, which is abolished in XIAP(-/-) cells. Therefore, orchestration of an IAP-IAP complex regulates apoptosis.