Cuz1/Ynl155w, a Zinc-Dependent Ubiquitin Binding Protein, Protects Cells from Metalloid-Induced Proteotoxicity [Cell Biology]

December 2nd, 2013 by Hanna, J., Waterman, D., Isasa, M., Elsasser, S., Shi, Y., Gygi, S., Finley, D.

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 multi-component 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.