UBE2S drives elongation of K11-linked ubiquitin chains by the Anaphase-Promoting Complex
UBE2S drives elongation of K11-linked ubiquitin chains by the Anaphase-Promoting Complex
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DOI：
10.1073/pnas.0912802107
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发表时间：
2010-01-26
影响因子：
11.1
通讯作者：
Kirschner, Marc W.
中科院分区：
文献类型：
--
作者：
Wu, Tao;Merbl, Yifat;Kirschner, Marc W.
后期促进复合体（APC）是一种E3泛素连接酶，通过依次靶向泛素化和蛋白酶体降解的细胞周期调节因子来调节有丝分裂和G1。APC形成泛素链的机制和由此产生的链拓扑结构仍然存在争议。通过使用单赖氨酸APC底物解剖泛素化底物的拓扑结构，我们发现APC催化的泛素化对泛素的K11键具有内在的偏好，这对于底物降解是必不可少的。K11特异性由E2酶UBE2S/E2- epf决定，该酶在底物被UbcH10或UbcH5预泛素化后延长泛素链。UBE2S与APC混合；在功能细胞周期提取物中，显性阴性Ube2S减缓APC底物降解。我们认为Ube2S是APC泛素化途径的一个关键而独特的组成部分。
The Anaphase-Promoting Complex (APC) is an E3 ubiquitin ligase that regulates mitosis and G1 by sequentially targeting cell-cycle regulators for ubiquitination and proteasomal degradation. The mechanism of ubiquitin chain formation by APC and the resultant chain topology remains controversial. By using a single-lysine APC substrate to dissect the topology of ubiquitinated substrates, we find that APC-catalyzed ubiquitination has an intrinsic preference for the K11 linkage of ubiquitin that is essential for substrate degradation. K11 specificity is determined by an E2 enzyme, UBE2S/E2-EPF, that elongates ubiquitin chains after the substrates are pre-ubiquitinated by UbcH10 or UbcH5. UBE2S copurifies with APC; dominant-negative Ube2S slows down APC substrate degradation in functional cell-cycle extracts. We propose that Ube2S is a critical, unique component of the APC ubiquitination pathway.