UMI, a Novel RNF168 Ubiquitin Binding Domain Involved in the DNA Damage Signaling Pathway
UMI, a Novel RNF168 Ubiquitin Binding Domain Involved in the DNA Damage Signaling Pathway
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DOI：
10.1128/mcb.00818-10
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发表时间：
2011-01-01
影响因子：
5.3
通讯作者：
Penengo, Lorenza
中科院分区：
文献类型：
--
作者：
Pinato, Sabrina;Gatti, Marco;Penengo, Lorenza
泛素化调节重要的细胞过程，包括DNA损伤反应(DDR)和DNA修复。泛素介导的信号的复杂性是由泛素受体解码的，泛素受体包含称为泛素结合域(UBD)的蛋白质模块。我们以前发现了一个新的泛素连接酶RNF168，它参与了DDR，并被赋予了两个UBD，命名为MIU(与泛素相互作用的基序)。在这里，我们鉴定了RNF168中存在的一种新的UBD，UMI(UIM和MIU相关的UBD)，并表征了以两个亮氨酸残基为中心的与泛素的相互作用表面。我们已经证明，除了MIU外，UMI的完整性对于RNF168的正确定位和包括组蛋白H2A在内的核蛋白的泛素化是必要的。最后，我们已经证明，UMI和MIU的同时失活阻止了关键的下游调节因子53BP1招募到DDR焦点。
Ubiquitination regulates important cellular processes, including the DNA damage response (DDR) and DNA repair. The complexity of the ubiquitin-mediated signals is decoded by ubiquitin receptors, which contain protein modules named ubiquitin binding domains (UBDs). We previously identified a new ubiquitin ligase, RNF168, involved in DDR and endowed with two UBDs named MIU (motif interacting with ubiquitin). Here we have provided the identification of a novel UBD, the UMI (UIM- and MIU-related UBD), present in RNF168, and characterized the interaction surface with ubiquitin, centered on two Leu residues. We have demonstrated that integrity of the UMI, in addition to the MIUs, is necessary for the proper localization of RNF168 and for ubiquitination of nuclear proteins, including histone H2A. Finally, we have shown that simultaneous inactivation of UMI and MIUs prevents the recruitment to DDR foci of the crucial downstream mediator 53BP1.