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Unexpectedly, a significant fraction (up to 22%) of hIAPP was found in the nuclear soluble and chromatin-enriched fractions of cultured human islet and rat insulinoma cells. The nucleolar accumulation of monomeric forms of hIAPP did not have any adverse effect on the proliferation of \u03b2-cells nor did it affect nucleolar organization or function. However, intact nucleolar organization and function were essential for hIAPP expression under normal and ER-stress conditions as RNA polymerase II inhibitor, \u03b1-amanitin, reduced hIAPP protein expression evoked by high glucose and thapsigargin. Promoter activity studies revealed the essential role of transcription factor FoxA2 in hIAPP promoter activation in ER-stressed \u03b2-cells. Transcriptome and secretory studies demonstrate that the biosynthetic and secretory capacity of islet \u03b2-cells was preserved during ER stress. Thus, the main reason for increased intracellular hIAPP accumulation is its enhanced biosynthesis under these adverse conditions.<\/jats:p>","DOI":"10.1042\/bcj20200984","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T11:02:31Z","timestamp":1614682951000},"page":"1261-1282","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["FoxA2 and RNA Pol II mediate human islet amyloid polypeptide turnover in ER-stressed pancreatic \u03b2-cells"],"prefix":"10.1042","volume":"478","author":[{"given":"Diti","family":"Chatterjee Bhowmick","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, The George Washington University, 800 22nd Street, N.W., Washington, DC 20052, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Burnett","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The George Washington University, 800 22nd Street, N.W., Washington, DC 20052, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanar","family":"Kudaibergenova","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The George Washington University, 800 22nd Street, N.W., Washington, DC 20052, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9350-0121","authenticated-orcid":false,"given":"Aleksandar M.","family":"Jeremic","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The George Washington University, 800 22nd Street, N.W., Washington, DC 20052, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,3,19]]},"reference":[{"issue":"Pt 20","key":"2021112218191951700_BCJ-2020-0984C1","doi-asserted-by":"publisher","first-page":"3381","DOI":"10.1242\/jcs.089110","article-title":"Protein localization in disease and therapy","volume":"124","year":"2011","journal-title":"J. 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