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.
Keywords:
Proteasome; Protein Degradation; Protein Misfolding; Stress Response; Ubiquitin.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Metalloids / pharmacology*
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Proteasome Endopeptidase Complex / genetics
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Proteasome Endopeptidase Complex / metabolism*
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Proteolysis / drug effects*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Stress, Physiological / drug effects*
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Stress, Physiological / genetics
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Ubiquitination / drug effects
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Ubiquitination / genetics
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Valosin Containing Protein
Substances
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Carrier Proteins
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Cell Cycle Proteins
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DNA-Binding Proteins
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Metalloids
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RPN4 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Proteasome Endopeptidase Complex
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Adenosine Triphosphatases
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CDC48 protein, S cerevisiae
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Valosin Containing Protein