NEDD8 modification of CUL1 short article dissociates p120CAND1, an inhibitor of CULl-SKP1 binding and SCIF ligases
NEDD8 modification of CUL1 short article dissociates p120CAND1, an inhibitor of CULl-SKP1 binding and SCIF ligases
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DOI：
10.1016/s1097-2765(02)00783-9
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发表时间：
2002-12-01
期刊：
影响因子：
16
通讯作者：
Xiong, Y
中科院分区：
文献类型：
--
作者：
Liu, JD;Furukawa, M;Xiong, Y
Cullin蛋白组装大量的RING E3泛素连接酶并调节各种生理过程。泛素样蛋白 NEDD8 对 cullin 进行共价修饰，通过一种尚未明确的机制激活 cullin 连接酶。我们在此表明，p120(CAND1) 选择性结合未neddylated CUL1，并通过CUL1 neddylation 解离。 CAND1与CUL1和ROC1形成三元复合物。 CAND1 将 SKP1 与 CUL1 解离，并在体外抑制 SCF 连接酶活性。体内抑制 CAND1 会增加 CUL1-SKP1 复合物的水平。我们认为，通过限制 SKP1-CUL1 相互作用，CAND1 调节生产性 SCF 泛素连接酶的组装，从而允许大量 SKP1-F 盒底物子复合物利用共同的 CUL1-ROC 核心。
Cullin proteins assemble a large number of RING E3 ubiquitin ligases and regulate various physiological processes. Covalent modification of cullins by the ubiquitin-like protein NEDD8 activates cullin ligases through an as yet undefined mechanism. We show here that p120(CAND1) selectively binds to unneddylated CUL1 and is dissociated by CUL1 neddylation. CAND1 formed a ternary complex with CUL1 and ROC1. CAND1 dissociated SKP1 from CUL1 and inhibited SCF ligase activity in vitro. Suppression of CAND1 in vivo increased the level of the CUL1-SKP1 complex. We suggest that by restricting SKP1-CUL1 interaction, CAND1 regulated the assembly of productive SCF ubiquitin ligases, allowing a common CUL1-ROC core to be utilized by a large number of SKP1-F box-substrate subcomplexes.