title: Cuz1/Ynl155w, a zinc-dependent ubiquitin-binding protein, protects cells from metalloid-induced proteotoxicity.
abstract: 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.
authors.affiliation: From the Department of Pathology, Brigham and Women's Hospital, and.
authors.forename: John
authors.initials: J
authors.lastname: Hanna
authors.forename: David
authors.initials: D
authors.lastname: Waterman
authors.forename: Marta
authors.initials: M
authors.lastname: Isasa
authors.forename: Suzanne
authors.initials: S
authors.lastname: Elsasser
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shi
authors.forename: Steven
authors.initials: S
authors.lastname: Gygi
authors.forename: Daniel
authors.initials: D
authors.lastname: Finley
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D058955:Metalloids / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects / Q000235:genetics; D000074405:Valosin Containing Protein
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D058955:Metalloids; C119430:RPN4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein
keywords: Proteasome; Protein Degradation; Protein Misfolding; Stress Response; Ubiquitin