DEDD and DEDD2 associate with caspase-8/10 and signal cell death
DEDD and DEDD2 associate with caspase-8/10 and signal cell death
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DOI：
10.1038/sj.onc.1206099
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发表时间：
2003-01-16
期刊：
影响因子：
8
通讯作者：
Yang, XL
中科院分区：
文献类型：
--
作者：
Alcivar, A;Hu, SM;Yang, XL
由细胞表面死亡受体触发的凋亡信号通过由保守结构域如死亡效应结构域（DED）介导的蛋白质-蛋白质相互作用传播到细胞内区室。一个独特的单一DED蛋白家族，包括DEDD和DEDD 2，靶向核仁。然而，DEDD/DEDD 2在细胞凋亡中的作用仍然不太清楚。在这里，我们表明，DEDD和DEDD 2是高度保守的不同物种，他们是在各种类型的细胞凋亡的有效诱导剂。缺失分析表明DEDD 2的N端DED结构域和C端区域都可以诱导细胞凋亡。该家族的细胞死亡活性似乎与其核定位有关。DEDD和DEDD 2结合到两个串联的含DED的半胱天冬酶，半胱天冬酶-8和-10，它们被死亡受体所吸引。与该家族的核定位一致，胱天蛋白酶-8在CD 95诱导的细胞凋亡过程中易位至细胞核。DEDD和DEDD 2也很容易与自己和彼此联系。这些结果表明，DEDD和DEDD 2可能是死亡受体的重要介质，它们可能靶向细胞核的半胱天冬酶。
An apoptotic signal triggered by cell surface death receptors is disseminated to intracellular compartments through protein-protein interactions mediated by conserved domains such as the death effector domain (DED). A unique family of single DED-containing proteins, including DEDD and DEDD2, is targeted to the nucleolus. However, the role of DEDD/DEDD2 in apoptosis remains less understood. Here we show that DEDD and DEDD2 are highly conserved in diverse species, and that they are potent inducers of apoptosis in various cell types. Deletion analysis indicates that both the N-terminal DED domain and the C-terminal region of DEDD2 can induce apoptosis. The cell death activity of this family appears to be related to their nuclear localization. DEDD and DEDD2 bind to two tandem DED-containing caspases, caspase -8 and -10, that are engaged by death receptors. Consistent with the nuclear localization of this family, caspase-8 translocates to the nucleus during CD95-induced apoptosis. DEDD and DEDD2 also readily associate with themselves and with each other. These results suggest that DEDD and DEDD2 may be important mediators for death receptors and that they may target caspases to the nucleus.