{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T19:08:34Z","timestamp":1767812914293,"version":"3.49.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Retinoic acid receptor \u03b1 (RARA) is critical for spermatogenesis, as shown by a sterility phenotype observed in Rara knockout mice. RARA is important in both Sertoli and germ cells of the testis. Here, we demonstrate that a disulfide isomerase glucose-regulated protein 58 (GRp58) participates in the nuclear import and degradation of RARA in Sertoli cells. GRp58 interacted with RARA in the presence of all-trans retinoic acid (ATRA) ligand and, as a complex, it was translocated from the cytoplasm to the nucleus and, then with time, GRp58 dissociated from RARA and was found in the cytoplasm. The GRp58 RNAi treatment disrupted ATRA-dependent RARA nuclear localization, indicating the requirement of GRp58 for RARA nuclear localization. Moreover, treatment with sulfhydryl-modifying agents that oxidize SH-groups of cysteine residues to disulfide bonds abolished ATRA-mediated RARA nuclear localization, suggesting that the thiol oxidoreductase activity of GRp58 may be required for RARA nuclear import. Additionally, the proteasome inhibitor treatment resulted in the co-localization of GRp58 and RARA at the endoplasmic reticulum (ER), suggesting that GRp58 may bring RARA to the ER for the ER-associated degradation (ERAD) of RARA before it is de-coupled from RARA for recycling. In this regard, proteasome inhibitor treatment also increased the interaction of RARA with UBE2J2, an ERAD-associated ubiquitin E2 enzyme. Collectively, the results indicate that GRp58 may act as a molecular chaperone that alters the protein conformation of RARA for its delivery to the nucleus and, then with time, accompanies RARA to the ER for RARA ubiquitination and proteasome-mediated ERAD.<\/jats:p>","DOI":"10.1530\/rep-09-0527","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T21:45:59Z","timestamp":1265233559000},"page":"717-731","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":22,"title":["Disulfide isomerase glucose-regulated protein 58 is required for the nuclear localization and degradation of retinoic acid receptor \u03b1"],"prefix":"10.1093","volume":"139","author":[{"given":"Li","family":"Zhu","sequence":"first","affiliation":[]},{"given":"Nadine C","family":"Santos","sequence":"additional","affiliation":[]},{"given":"Kwan Hee","family":"Kim","sequence":"additional","affiliation":[]}],"member":"286","published-online":{"date-parts":[[2010,4,1]]},"reference":[{"key":"2026010712515844500_bib1","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1006\/bbrc.1993.1919","article-title":"Purification of a 57\u200akDa nuclear matrix protein associated with thiol:protein-disulfide oxidoreductase and phospholipase C activities","volume":"194","author":"Altieri","year":"1993","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"2026010712515844500_bib2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0303-7207(97)00115-9","article-title":"Inhibition of mineralocorticoid and glucocorticoid receptor function by the heat shock protein 90-binding agent geldanamycin","volume":"131","author":"Bamberger","year":"1997","journal-title":"Molecular and Cellular Endocrinology"},{"key":"2026010712515844500_bib3","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0074-7696(05)45004-4","article-title":"Cellular functions of endoplasmic reticulum chaperones calreticulin, calnexin, and ERp57","volume":"245","author":"Bedard","year":"2005","journal-title":"International Reviews of Cytology"},{"key":"2026010712515844500_bib4","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1002\/j.1460-2075.1996.tb00560.x","article-title":"Degradation of subunits of the Sec61p complex, an integral component of the ER membrane, by the ubiquitin\u2013proteasome pathway","volume":"15","author":"Biederer","year":"1996","journal-title":"EMBO Journal"},{"key":"2026010712515844500_bib5","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.tcb.2007.04.003","article-title":"Protein kinases and the proteasome join in the combinatorial control of transcription by nuclear retinoic acid receptors","volume":"17","author":"Bour","year":"2007","journal-title":"Trends in Cell Biology"},{"key":"2026010712515844500_bib6","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1074\/jbc.275.6.4145","article-title":"Follicle-stimulating hormone inhibits all-trans-retinoic acid-induced retinoic acid receptor alpha nuclear localization and transcriptional activation in mouse Sertoli cell lines","volume":"275","author":"Braun","year":"2000","journal-title":"Journal of Biological Chemistry"},{"key":"2026010712515844500_bib7","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1095\/biolreprod67.1.29","article-title":"Positive regulation of retinoic acid receptor alpha by protein kinase C and mitogen-activated protein kinase in sertoli cells","volume":"67","author":"Braun","year":"2002","journal-title":"Biology of Reproduction"},{"key":"2026010712515844500_bib8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0022-4731(89)90060-5","article-title":"Interaction of the chicken progesterone receptor with heat shock protein (HSP) 90","volume":"34","author":"Carson-Jurica","year":"1989","journal-title":"Journal of Steroid Biochemistry"},{"key":"2026010712515844500_bib9","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1096\/fasebj.10.9.8801176","article-title":"A decade of molecular biology of retinoic acid receptors","volume":"10","author":"Chambon","year":"1996","journal-title":"FASEB Journal"},{"key":"2026010712515844500_bib10","doi-asserted-by":"crossref","first-page":"20686","DOI":"10.1016\/S0021-9258(17)30558-6","article-title":"Several regions of human estrogen receptor are involved in the formation of receptor-heat shock protein 90 complexes","volume":"265","author":"Chambraud","year":"1990","journal-title":"Journal of Biological Chemistry"},{"key":"2026010712515844500_bib11","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1210\/endo.143.2.8618","article-title":"Identification of a novel gene product. 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