Cuz1/Ynl155w, a Zinc-dependent Ubiquitin-binding Protein, Protects Cells from Metalloid-induced Proteotoxicity

Abstract

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.