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Publication : Selenoprotein T is a novel OST subunit that regulates UPR signaling and hormone secretion.

First Author  Hamieh A Year  2017
Journal  EMBO Rep Volume  18
Issue  11 Pages  1935-1946
PubMed ID  28928140 Mgi Jnum  J:252321
Mgi Id  MGI:5927130 Doi  10.15252/embr.201643504
Citation  Hamieh A, et al. (2017) Selenoprotein T is a novel OST subunit that regulates UPR signaling and hormone secretion. EMBO Rep 18(11):1935-1946
abstractText  Selenoprotein T (SelT) is a recently characterized thioredoxin-like protein whose expression is very high during development, but is confined to endocrine tissues in adulthood where its function is unknown. We report here that SelT is required for adaptation to the stressful conditions of high hormone level production in endocrine cells. Using immunofluorescence and TEM immunogold approaches, we find that SelT is expressed at the endoplasmic reticulum membrane in all hormone-producing pituitary cell types. SelT knockdown in corticotrope cells promotes unfolded protein response (UPR) and ER stress and lowers endoplasmic reticulum-associated protein degradation (ERAD) and hormone production. Using a screen in yeast for SelT-membrane protein interactions, we sort keratinocyte-associated protein 2 (KCP2), a subunit of the protein complex oligosaccharyltransferase (OST). In fact, SelT interacts not only with KCP2 but also with other subunits of the A-type OST complex which are depleted after SelT knockdown leading to POMC N-glycosylation defects. This study identifies SelT as a novel subunit of the A-type OST complex, indispensable for its integrity and for ER homeostasis, and exerting a pivotal adaptive function that allows endocrine cells to properly achieve the maturation and secretion of hormones.
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