FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex
FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex
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DOI：
10.1016/s0092-8674(00)81266-0
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发表时间：
1996-06-14
期刊：
影响因子：
64.5
通讯作者：
Dixit, VM
中科院分区：
文献类型：
--
作者：
Muzio, M;Chinnaiyan, AM;Dixit, VM
为了鉴定CD95(Fas/APO-1)死亡诱导信号复合体的CAP3和CAP4组分，我们使用了纳米电喷雾串联质谱仪，这是一种新近发展起来的技术，可以对大量的聚丙烯酰胺凝胶分离蛋白进行测序。有趣的是，CAP4编码一个新的55 kDa的蛋白，命名为FLICE，它与FADD和ICE/CED-3半胱氨酸蛋白酶家族具有同源性。Flice结合FADD的死亡效应结构域，在过度表达时诱导细胞凋亡，这一过程被ICE家族抑制剂CrmA和z-VAD-fmk所阻断。CAP3被鉴定为FLICE原结构域，在蛋白水解性激活后可能仍与受体结合。综上所述，这是将死亡受体与ICE/CED-3家族的促凋亡蛋白酶物理联系起来的独特的生化证据。
To identify CAP3 and CAP4 components of the CD95 (Fas/APO-1) death-inducing signaling complex, we utilized nano-electrospray tandem mass spectrometry, a recently developed technique to sequence femtomole quantities of polyacrylamide gel-separated proteins. Interestingly, CAP4 encodes a novel 55 kDa protein, designated FLICE, which has homology to both FADD and the ICE/CED-3 family of cysteine proteases. FLICE binds to the death effector domain of FADD and upon overexpression induces apoptosis that is blocked by the ICE family inhibitors, CrmA and z-VAD-fmk. CAP3 was identified as the FLICE prodomain which likely remains bound to the receptor after proteolytic activation. Taken together, this is unique biochemical evidence to link a death receptor physically to the proapoptotic proteases of the ICE/CED-3 family.