Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT transcription repressor complex

被引:172
作者
Albert, TK
Hanzawa, H
Legtenberg, YIA
de Ruwe, MJ
van den Heuvel, FAJ
Collart, MA
Boelens, R
Timmers, HTM [1 ]
机构
[1] Univ Med Ctr, Physiol Chem Lab, NL-3508 AB Utrecht, Netherlands
[2] Univ Utrecht, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands
[3] Univ Geneva, CMU, Dept Biochem Med, CH-1211 Geneva, Switzerland
关键词
CCR4-NOT complex; RING finger; TFIID; transcription regulation; ubiquitin-protein ligase;
D O I
10.1093/emboj/21.3.355
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The RING finger protein CNOT4 is a component of the CCR4-NOT complex. This complex is implicated in repression of RNA polymerase II transcription. Here we demonstrate that CNOT4 functions as a ubiquitin-protein ligase (E3). We show that the unique C4C4 RING domain of CNOT4 interacts with a subset of ubiquitin-conjugating enzymes (E2s). Using NMR spectroscopy, we detail the interaction of CNOT4 with UbcH5B and characterize RING residues that are critical for this interaction. CNOT4 acts as a potent E3 ligase in vitro. Mutations that destabilize the E2-E3 interface abolish this activity. Based on these results, we present a model of how E3 ligase function within the CCR4-NOT complex relates to transcriptional regulation.
引用
收藏
页码:355 / 364
页数:10
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