Conserved function of RNF4 family proteins in eukaryotes: targeting a ubiquitin ligase to SUMOylated proteins
Conserved function of RNF4 family proteins in eukaryotes: targeting a ubiquitin ligase to SUMOylated proteins
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DOI：
10.1038/sj.emboj.7601839
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发表时间：
2007-09-19
期刊：
影响因子：
11.4
通讯作者：
Hunter, Tony
中科院分区：
文献类型：
--
作者：
Sun, Huaiyu;Leverson, Joel D.;Hunter, Tony
小泛蛋白样修饰物（SUMO）结合蛋白的功能是了解SUMO化如何调节细胞过程的关键。我们鉴定了两个相关的粟酒裂殖酵母蛋白，Rfp 1和Rfp 2，每个都具有N-末端SUMO相互作用基序（SIM）和C-末端RING-指结构域。遗传分析表明，Rfp 1和Rfp 2具有冗余功能;它们共同对细胞生长和基因组稳定性至关重要。哺乳动物RNF 4是一种活性泛素E3连接酶，是Rfp 1/Rfp 2的直向同源物。Rfp 1和Rfp 2缺乏E3活性，但通过RING - RING相互作用募集活性RING-指泛素连接酶Slx 8，以形成功能性E3。RNF 4补充了rfp 1 rfp 2、slx 8和rfp 1 rfp 2slx 8突变细胞的生长和基因组稳定性缺陷。Rfp-Slx 8复合物和RNF 4在体外以SUMO结合依赖性方式特异性泛素化含SUMO的人工底物. SUMO化蛋白在rfp 1 rfp 2双无效细胞中积累，表明Rfp/Slx 8蛋白可能促进SUMO化靶标的泛素依赖性降解。因此，我们描述了一个含有SIM的环指蛋白家族，该家族通过连接SUMO相互作用和泛素结合来潜在地调节真核生物基因组的稳定性。
The function of small ubiquitin- like modifier ( SUMO)binding proteins is key to understanding how SUMOylation regulates cellular processes. We identified two related Schizosaccharomyces pombe proteins, Rfp1 and Rfp2, each having an N- terminal SUMO- interacting motif ( SIM) and a C- terminal RING- finger domain. Genetic analysis shows that Rfp1 and Rfp2 have redundant functions; together, they are essential for cell growth and genome stability. Mammalian RNF4, an active ubiquitin E3 ligase, is an orthologue of Rfp1/ Rfp2. Rfp1 and Rfp2 lack E3 activity but recruit Slx8, an active RING- finger ubiquitin ligase, through a RING - RING interaction, to form a functional E3. RNF4 complements the growth and genomic stability defects of rfp1rfp2, slx8, and rfp1rfp2slx8 mutant cells. Both the Rfp- Slx8 complex and RNF4 specifically ubiquitylate artificial SUMO- containing substrates in vitro in a SUMO binding- dependent manner. SUMOylated proteins accumulate in rfp1rfp2 double- null cells, suggesting that Rfp/ Slx8 proteins may promote ubiquitin- dependent degradation of SUMOylated targets. Hence, we describe a family of SIM- containing RING- finger proteins that potentially regulates eukaryotic genome stability through linking SUMO- interaction with ubiquitin conjugation.