Distinct modes of regulation of the Uch37 deubiquitinating enzyme in the proteasome and in the Ino80 chromatin-remodeling complex.
Distinct modes of regulation of the Uch37 deubiquitinating enzyme in the proteasome and in the Ino80 chromatin-remodeling complex.
复制标题
DOI：
10.1016/j.molcel.2008.08.027
复制
发表时间：
2008-09-26
期刊：
影响因子：
16
通讯作者：
Conaway, Joan W.
中科院分区：
文献类型：
--
作者：
Yao, Tingting;Song, Ling;Jin, Jingji;Cai, Yong;Takahashi, Hidehisa;Swanson, Selene K.;Washburn, Michael P.;Florens, Laurence;Conaway, Ronald C.;Cohen, Robert E.;Conaway, Joan W.
去泛素化酶（DUBs）是通过分解泛素-蛋白质缀合物来拮抗泛素介导的信号传导的蛋白酶。DUB如何在体内调节以及它们的底物特异性如何实现在很大程度上是未知的。保守的DUB Uch 37在从裂殖酵母到人类的生物体中的蛋白酶体上发现。Uch 37的去泛素化作用被蛋白酶体结合激活，这使得Uch 37能够加工多聚泛素链。在这里，我们表明，在细胞核Uch 37也与人类Ino80染色质重塑复合物（hINO80）。在hINO80中，Uch37保持在非活性状态;然而，它可以通过Ino80复合物与蛋白酶体的瞬时相互作用而被激活。因此，DUB活动可以通过与伴侣蛋白的动态相互作用进行正向和负向调节。此外，我们的研究结果表明，蛋白酶体和hINO 80染色质重塑复合物可能合作调节转录或DNA修复，这两种复合物都参与其中。
Deubiquitinating enzymes (DUBs) are proteases that can antagonize ubiquitin-mediated signalling by disassembling ubiquitin-protein conjugates. How DUBs are regulated in vivo and how their substrate specificities are achieved are largely unknown. The conserved DUB Uch37 is found on proteasomes in organisms ranging from fission yeast to humans. Deubiquitination by Uch37 is activated by proteasomal binding, which enables Uch37 to process polyubiquitin chains. Here we show that in the nucleus Uch37 is also associated with the human Ino80 chromatin-remodeling complex (hINO80). In hINO80, Uch37 is held in an inactive state; however, it can be activated by transient interaction of the Ino80 complex with the proteasome. Thus, DUB activities can be modulated both positively and negatively via dynamic interactions with partner proteins. In addition, our findings suggest that the proteasome and the hINO80 chromatin-remodeling complex may cooperate to regulate transcription or DNA repair, processes in which both complexes have been implicated.
登录
查看更多内容
影响因子：
2.9
作者：
Case, A;Stein, RL
通讯作者：
Stein, RL
影响因子：
2.9
作者：
Rajesh, S;Sakamoto, T;Ito, Y
通讯作者：
Ito, Y
影响因子：
5.3
作者：
Lee, KK;Florens, L;Workman, JL
通讯作者：
Workman, JL
影响因子：
16
作者：
Pickart, CM
通讯作者：
Pickart, CM
影响因子：
16
作者：
Lassot, Irina;Latreille, Daniel;Kiernan, Rosemary E.
通讯作者：
Kiernan, Rosemary E.