{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T06:46:31Z","timestamp":1792219591253,"version":"4.4.0"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,9,9]],"date-time":"2013-09-09T00:00:00Z","timestamp":1378684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2013,11]]},"abstract":"Summary<\/jats:title>Accumulation of proteins in the endoplasmic reticulum (ER<\/jats:styled-content>) typically induces stress and initiates the unfolded protein response (UPR<\/jats:styled-content>) to facilitate recovery. If homeostasis is not restored, apoptosis is induced. However, adaptation to chronic UPR<\/jats:styled-content> activation can increase resistance to subsequent acute ER<\/jats:styled-content> stress. We therefore investigated adaptive mechanisms in O<\/jats:styled-content>culocutaneous albinism type 2<\/jats:italic> (Oca2<\/jats:italic><\/jats:styled-content>)\u2010null melanocytes where UPR<\/jats:styled-content> signaling is arrested despite continued tyrosinase accumulation leading to resistance to the chemical ER<\/jats:styled-content> stressor thapsigargin. Although thapsigargin triggers UPR<\/jats:styled-content> activation, instead of Perk\u2010mediated phosphorylation of eIF<\/jats:styled-content>2\u03b1, in Oca2<\/jats:italic><\/jats:styled-content>\u2010null melanocytes, eIF<\/jats:styled-content>2\u03b1 was rapidly dephosphorylated upon treatment. Dephosphorylation was mediated by the Gadd34\u2010PP<\/jats:styled-content>1\u03b1 phosphatase complex. Gadd34\u2010complex inhibition blocked eIF<\/jats:styled-content>2\u03b1 dephosphorylation and significantly increased Oca2<\/jats:italic><\/jats:styled-content>\u2010null melanocyte sensitivity to thapsigargin. Thus, Oca2<\/jats:italic><\/jats:styled-content>\u2010null melanocytes adapt to acute ER<\/jats:styled-content> stress by disruption of pro\u2010apoptotic Perk signaling, which promotes cell survival. This is the first study to demonstrate rapid eIF<\/jats:styled-content>2\u03b1 dephosphorylation as an adaptive mechanism to ER<\/jats:styled-content> stress.<\/jats:p>","DOI":"10.1111\/pcmr.12158","type":"journal-article","created":{"date-parts":[[2013,8,21]],"date-time":"2013-08-21T05:30:44Z","timestamp":1377063044000},"page":"826-834","source":"Crossref","is-referenced-by-count":16,"title":["Loss of Oca2<\/i><\/scp> disrupts the unfolded protein response and increases resistance to endoplasmic reticulum stress in melanocytes"],"prefix":"10.1111","volume":"26","author":[{"given":"Tsing","family":"Cheng","sequence":"first","affiliation":[{"name":"The Ronald O. Perelman Department of Dermatology New York University School of Medicine New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth J.","family":"Orlow","sequence":"additional","affiliation":[{"name":"The Ronald O. Perelman Department of Dermatology New York University School of Medicine New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashiela","family":"Manga","sequence":"additional","affiliation":[{"name":"The Ronald O. 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