UBE2S drives elongation of K11-linked ubiquitin chains by the Anaphase-Promoting Complex

被引:188
作者
Wu, Tao [1 ]
Merbl, Yifat [1 ]
Huo, Ying [2 ]
Gallop, Jennifer L. [1 ]
Tzur, Amit [1 ]
Kirschner, Marc W. [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA
[2] Jilin Univ, Sch Pharm, Changchun 130021, Jilin Province, Peoples R China
关键词
E2; enzyme; E3; ligase; proteasome; cell cycle; mitosis; CARRIER PROTEIN; POLYUBIQUITIN CHAINS; CONJUGATING ENZYMES; MITOTIC CYCLINS; APC; IDENTIFICATION; DEGRADATION; CHECKPOINT; DESTRUCTION; MECHANISM;
D O I
10.1073/pnas.0912802107
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1355 / 1360
页数:6
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