{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T10:40:00Z","timestamp":1769164800380,"version":"3.49.0"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,3,27]],"date-time":"2012-03-27T00:00:00Z","timestamp":1332806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Aims\/Introduction:\u2002<\/jats:bold> Mutations in hepatocyte nuclear factor\u20104\u03b1 (HNF4\u03b1) lead to various diseases, among which C\u2010terminal deletions of HNF4\u03b1 are exclusively responsible for maturity onset diabetes of the young 1 (MODY1). MODY is an autosomal dominant disease characterized by a primary defect in insulin response to glucose, suggesting that the C\u2010terminus of HNF4\u03b1 is important for pancreatic \u03b2\u2010cell function. To clarify the role of the C\u2010terminus of HNF4\u03b1, changes in cellular localization and the binding ability to its regulator were examined, specifically in the region containing Q268, which deletion causes MODY1.<\/jats:p><jats:p><jats:bold>Materials and Methods:\u2002<\/jats:bold> Cellular localization of mutant HNF4\u03b1 were examined in monkey kidney 7 (COS7), Chinese hamster ovary, rat insulinoma and mouse insulinoma cells, and their binding activity to other proteins were examined by fluorescence resonance energy transfer (FRET) in COS7 cells.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Although wild\u2010type HNF4\u03b1 was localized in the nucleoplasm in transfected cultured cells, Q268X\u2010HNF4\u03b1 was located predominantly in the nucleolus. Deletion analysis of the C\u2010terminus of HNF4\u03b1 showed that the S337X\u2010HNF4\u03b1 mutant, and other mutants with shorter amino acid sequences (S337\u2010K194), were mostly localized in the nucleolus. HNF4\u03b1 mutants with amino acid sequences shorter than the W192X\u2010HNF4\u03b1 mutant gradually spread to the nucleoplasm in accordance with their lengths. The A250X\u2010HNF4\u03b1 mutant was capable of causing the accumulation of HNF4\u03b1 or the small heterodimer partner (SHP), one of the HNF4\u03b1 regulators, in the nucleolus. However, the R154X\u2010HNF4\u03b1 mutant did not have binding ability to wild\u2010type HNF4\u03b1 or SHP, and thus was seen in the nucleus.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> The C\u2010terminus sites might play a key role in facilitating the nucleolar and subnucleolar localization of HNF4\u03b1. <jats:bold>(J Diabetes Invest, doi: 10.1111\/j.2040\u20101124.2012.00210.x, 2012)<\/jats:bold><\/jats:p>","DOI":"10.1111\/j.2040-1124.2012.00210.x","type":"journal-article","created":{"date-parts":[[2012,3,27]],"date-time":"2012-03-27T22:04:30Z","timestamp":1332885870000},"page":"449-456","source":"Crossref","is-referenced-by-count":4,"title":["Localization of hepatocyte nuclear factor\u20104\u03b1 in the nucleolus and nucleus is regulated by its C\u2010terminus"],"prefix":"10.1111","volume":"3","author":[{"given":"Makiko","family":"Ogata","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeo","family":"Awaji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoko","family":"Iwasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Risa","family":"Fujimaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miho","family":"Takizawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graeme 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