Regulation of the Polycomb protein RING1B ubiquitination by USP7
Regulation of the Polycomb protein RING1B ubiquitination by USP7
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DOI：
10.1016/j.bbrc.2010.08.082
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发表时间：
2010-09-24
影响因子：
3.1
通讯作者：
Ciechanover, Aaron
中科院分区：
文献类型：
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作者：
de Bie, Prim;Zaaroor-Regev, Daphna;Ciechanover, Aaron
E3泛素连接酶RING 1B在通过单泛素化组蛋白H2 A的Polycomb介导的基因沉默中起重要作用。RING 1B的活性和稳定性都以两种不同的方式受到泛素化的控制。RING 1B的自身泛素化产生基于K6、K27和K48的混合多聚泛素链，并且是其作为连接酶的活性所必需的。其蛋白酶体降解由另一种连接酶E6-AP介导，E6-AP催化基于K48的链的形成。由于这两种泛素化模式靶向相同的赖氨酸残基并因此相互排斥，RING 1B的重要调节模式应该是在去泛素化水平。在此我们将USP 7鉴定为调节RING 1B的泛素化状态的去泛素化酶RING 1B与USP 7相互作用，其部分由其RING结构域介导。USP 7与其他Polycomb蛋白形成复合物。提示在调节这些复合物中的广泛作用虽然USP 7在体外和体内直接特异性地去泛素化RING 1B，但它不区分泛素化的激活和蛋白水解靶向模式，因此对RING 1B具有稳定作用。(C)2010爱思唯尔公司版权所有
The E3 ubiquitin ligase RING1B plays an important role in Polycomb-mediated gene silencing by mono-ubiquitinating histone H2A Both the activity and stability of RING1B are controlled by ubiquitination in two distinct manners Self ubiquitination of RING1B generates K6, K27 and K48-based mixed polyubiquitin chain, and is required for its activity as a ligase On the other hand, its proteasomal degradation is mediated by another ligase, E6-AP catalyzes the formation of K48-based chains Since these two modes of ubiquitination target the same lysine residues and are therefore mutually exclusive, an Important mode of regulation of RING1B should be at the level of deubiquitination Here we identify USP7 as a deubiquitinating enzyme that regulates the ubiquitination state of RING1B RING1B interacts with USP7, which is mediated in part by its RING domain In addition. USP7 was found in a complex with other Polycomb proteins. suggesting a broad role in regulating these complexes Although, USP7 directly and specifically deubiquitinates RING1B in vitro and in vivo, it does not discriminate between the activating and proteolysis-targeting modes of ubiquitination, and therefore has a stabilizing effect on RING1B. (C) 2010 Elsevier Inc All rights reserved