Wss1 is a SUMO-dependent isopeptidase that interacts genetically with the Slx5-Slx8 SUMO-targeted ubiquitin ligase.
Wss1 is a SUMO-dependent isopeptidase that interacts genetically with the Slx5-Slx8 SUMO-targeted ubiquitin ligase.
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Wss1 是一种 SUMO 依赖性肽酶，与 Slx5-Slx8 SUMO 靶向泛素连接酶发生遗传相互作用。
DOI：
10.1128/mcb.01649-09
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发表时间：
2010
影响因子：
5.3
通讯作者：
Brill,StevenJ
中科院分区：
文献类型：
--
作者：
Mullen,JanetR;Chen,Chi-Fu;Brill,StevenJ
蛋白质苏酰化在控制基因组完整性方面发挥着重要但人们知之甚少的作用。在酿酒酵母中，Slx5-Slx8 SUMO 靶向 Ub 连接酶似乎需要泛素化在缺乏 Sgs1 DNA 解旋酶的情况下产生的 sumoylated 蛋白。WSS1 是突变体 SUMO 的高拷贝数抑制因子，与该途径有关，因为它与 SLX5-SLX8 突变体（包括 awss1Δ）具有相同的表型sgs1Δ综合适应性缺陷。在这里，我们展示了 Wss1（一种推定的金属蛋白酶）物理结合 SUMO 并在聚 SUMO 链上表现出体外异肽酶活性。与 SLX5 一样，WSS1 的过表达会抑制 sgs1Δ slx5Δ 致死率和 ulp1ts 生长缺陷。有趣的是，尽管 Wss1 对泛素化底物和多聚 Ub 链相对无活性，但它能有效地使 Ub-SUMO 异肽缀合物和 Ub-SUMO 融合蛋白去泛素化。基于 Wss1 与蛋白酶体亚基的物理关联，Wss1 进一步参与 Ub 代谢。结果表明，Wss1 是一种 SUMO 依赖性肽酶，在蛋白酶体降解时作用于 sumoylated 底物。
Protein sumoylation plays an important but poorly understood role in controlling genome integrity. InSaccharomyces cerevisiae, the Slx5-Slx8 SUMO-targeted Ub ligase appears to be needed to ubiquitinate sumoylated proteins that arise in the absence of the Sgs1 DNA helicase.WSS1, a high-copy-number suppressor of a mutant SUMO, was implicated in this pathway because it shares phenotypes withSLX5-SLX8mutants, including awss1Δ sgs1Δsynthetic-fitness defect. Here we show that Wss1, a putative metalloprotease, physically binds SUMO and displaysin vitroisopeptidase activity on poly-SUMO chains. Like that ofSLX5, overexpression ofWSS1suppressessgs1Δ slx5Δlethality and theulp1tsgrowth defect. Interestingly, although Wss1 is relatively inactive on ubiquitinated substrates and poly-Ub chains, it efficiently deubiquitinates a Ub-SUMO isopeptide conjugate and a Ub-SUMO fusion protein. Wss1 was further implicated in Ub metabolism on the basis of its physical association with proteasomal subunits. The results suggest that Wss1 is a SUMO-dependent isopeptidase that acts on sumoylated substrates as they undergo proteasomal degradation.