{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:09:12Z","timestamp":1782367752838,"version":"3.54.5"},"reference-count":26,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM105958"],"award-info":[{"award-number":["R01 GM105958"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 GM007273"],"award-info":[{"award-number":["T32 GM007273"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["Graduate Student Fellowship"],"award-info":[{"award-number":["Graduate Student Fellowship"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Unfavorable redox conditions in the endoplasmic reticulum (ER) can decrease the capacity for protein secretion, altering vital cell functions. While systems to manage reductive stress are well-established, how cells cope with an overly oxidizing ER remains largely undefined. In previous work (Wang et al., 2014), we demonstrated that the chaperone BiP is a sensor of overly oxidizing ER conditions. We showed that modification of a conserved BiP cysteine during stress beneficially alters BiP chaperone activity to cope with suboptimal folding conditions. How this cysteine is reduced to reestablish 'normal' BiP activity post-oxidative stress has remained unknown. Here we demonstrate that BiP's nucleotide exchange factor \u2013 Sil1 \u2013 can reverse BiP cysteine oxidation. This previously unexpected reductant capacity for yeast Sil1 has potential implications for the human ataxia Marinesco-Sj\u00f6gren syndrome, where it is interesting to speculate that a disruption in ER redox-signaling (due to genetic defects in SIL1) may influence disease pathology.<\/jats:p>","DOI":"10.7554\/elife.24141","type":"journal-article","created":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T08:00:16Z","timestamp":1488528016000},"source":"Crossref","is-referenced-by-count":28,"title":["An unexpected role for the yeast nucleotide exchange factor Sil1 as a reductant acting on the molecular chaperone BiP"],"prefix":"10.7554","volume":"6","author":[{"given":"Kevin D","family":"Siegenthaler","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Cornell University, Ithaca, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristeen A","family":"Pareja","sequence":"additional","affiliation":[{"name":"Department of Molecular 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