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These observations raise the question of whether a DUB can control the fate of a nonubiquitinated ERAD substrate. In this study, we probed the role of the ERAD-associated DUB, YOD1, during retro-translocation of the nonubiquitinated cholera toxin A1 (CTA1) peptide, a critical intoxication step. Through combining knockdown, overexpression, and binding studies, we demonstrated that YOD1 negatively controls CTA1 retro-translocation, likely by deubiquitinating and inactivating ubiquitinated ERAD components that normally promote toxin retro-translocation. YOD1 also antagonizes the proteasomal degradation of nonglycosylated pro-\u03b1 factor, a postulated nonubiquitinated yeast ERAD substrate, in mammalian cells. Our findings reveal that a cytosolic DUB exerts a negative function during retro-translocation of nonubiquitinated substrates, potentially by acting on elements of the ERAD machinery.<\/jats:p>","DOI":"10.1091\/mbc.e13-06-0332","type":"journal-article","created":{"date-parts":[[2013,9,26]],"date-time":"2013-09-26T03:03:19Z","timestamp":1380164599000},"page":"3545-3556","source":"Crossref","is-referenced-by-count":31,"title":["A deubiquitinase negatively regulates retro-translocation of nonubiquitinated substrates"],"prefix":"10.1091","volume":"24","author":[{"given":"Kaleena M.","family":"Bernardi","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 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