Cuz1/Ynl155w, a Zinc-dependent Ubiquitin-binding Protein, Protects Cells from Metalloid-induced Proteotoxicity
Cuz1/Ynl155w, a Zinc-dependent Ubiquitin-binding Protein, Protects Cells from Metalloid-induced Proteotoxicity
复制标题
DOI：
10.1074/jbc.m113.534032
复制
发表时间：
2014-01-17
影响因子：
4.8
通讯作者：
Finley, Daniel
中科院分区：
文献类型：
--
作者：
Hanna, John;Waterman, David;Finley, Daniel
背景：蛋白质错误折叠是对细胞的普遍威胁，是由泛素-蛋白酶体系统处理的。结果：Ynl155w是一种锌依赖性泛素结合蛋白，与蛋白酶体和Cdc48相互作用，是类金属存活所必需的。结论：Ynl155w可能通过向Cdc48和蛋白酶体传递泛素化蛋白来保护细胞免受金属诱导的蛋白质毒性。意义：Ynl155w代表了错误折叠蛋白的一种新的应激反应因子。蛋白质错误折叠是对细胞的普遍威胁。泛素-蛋白酶体系统介导细胞应激反应，能够消除错误折叠的蛋白质。在这里，我们确定Cuz1/Ynl155w是泛素系统的一个组成部分，能够与蛋白酶体和Cdc48相互作用。Cuz1/Ynl155w受转录因子Rpn4调控，是细胞暴露于三价类金属砷和锑下存活所必需的。一个相关蛋白Yor052c也显示出类似的表型，表明这是一个多组分的应激反应途径。Cuz1/Ynl155w是一种锌依赖性泛素结合蛋白。因此，Cuz1/Ynl155w被认为可以通过将泛素化底物传递到Cdc48和蛋白酶体进行破坏来保护细胞免受金属诱导的蛋白质毒性。
Background: Protein misfolding, a universal threat to cells, is dealt with by the ubiquitin-proteasome system. Results: Ynl155w is a zinc-dependent ubiquitin-binding protein, interacts with proteasome and Cdc48, and is essential for surviving metalloids. Conclusion: Ynl155w may protect cells from metalloid-induced proteotoxicity by delivering ubiquitinated proteins to Cdc48 and proteasome. Significance: Ynl155w represents a novel stress response factor for misfolded proteins.Protein misfolding is a universal threat to cells. The ubiquitin-proteasome system mediates a cellular stress response capable of eliminating misfolded proteins. Here we identify Cuz1/Ynl155w as a component of the ubiquitin system, capable of interacting with both the proteasome and Cdc48. Cuz1/Ynl155w is regulated by the transcription factor Rpn4, and is required for cells to survive exposure to the trivalent metalloids arsenic and antimony. A related protein, Yor052c, shows similar phenotypes, suggesting a multicomponent stress response pathway. Cuz1/Ynl155w functions as a zinc-dependent ubiquitin-binding protein. Thus, Cuz1/Ynl155w is proposed to protect cells from metalloid-induced proteotoxicity by delivering ubiquitinated substrates to Cdc48 and the proteasome for destruction.