{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:24:13Z","timestamp":1777393453881,"version":"3.51.4"},"reference-count":0,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T00:00:00Z","timestamp":1412899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2014,10,10]]},"abstract":"<jats:p>Proteolytic processing of the amyloid-\u03b2 protein precursor (A\u03b2PP) occurs via alternative pathways, culminating with the production of the A\u03b2PP intracellular domain (AICD). AICD can translocate to the nucleus and regulate transcription, but its activity is modulated by interactions with other proteins. In the nucleus, AICD, FE65, and Tip60 associate into AFT complexes, which are targeted to nuclear spots which correspond to transcription factories. Here we report that RanBP9 interacts with the cytoplasmic domain of A\u03b2PP, through the NPXY internalization motif. Moreover, RanBP9 interaction with Tip60 is also described. The RanBP9-Tip60 interaction dramatically relocated RanBP9 from a widespread cellular distribution to nuclear speckles. A\u03b2PP processing is a central aspect in determining the protein's function and that of its resulting proteolytic fragments, among them AICD. The latter results from the amyloidogenic pathway and is the peptidic species predominantly involved in nuclear signaling. Of note RanBP9 transfection was previously demonstrated to increase amyloid-\u03b2 generation. Here we show that RanBP9 relocates AICD to the Tip60-enriched nuclear speckles, and prevented the formation of nuclear spots formation, having therefore a negative effect on AICD mediated nuclear signaling and consequently AFT complex formation. Furthermore, by transfecting cells with increasing amounts of RanBP9, the expression of AICD-regulated genes, including A\u03b2PP itself, was reduced. Given the data presented, one can deduce that RanBP9 has an inhibitory regulatory effect on AICD-mediated transcription and the effect is mediated by relocating AICD away from transcription factories.<\/jats:p>","DOI":"10.3233\/jad-132495","type":"journal-article","created":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T13:14:19Z","timestamp":1528118059000},"page":"1415-1433","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["RanBP9 Modulates AICD Localization and Transcriptional Activity via Direct Interaction with Tip60"],"prefix":"10.1177","volume":"42","author":[{"given":"Sara C.","family":"Domingues","sequence":"first","affiliation":[{"name":"Centre for Cell Biology, Health Sciences Department and Biology Department, University of Aveiro, Aveiro, Portugal"}]},{"given":"Uwe","family":"Konietzko","sequence":"additional","affiliation":[{"name":"Division of Psychiatry Research, University of Zurich, Zurich, Switzerland"}]},{"given":"Ana Gabriela","family":"Henriques","sequence":"additional","affiliation":[{"name":"Centre for Cell Biology, Health Sciences Department and Biology Department, University of Aveiro, Aveiro, Portugal"}]},{"given":"Sandra","family":"Rebelo","sequence":"additional","affiliation":[{"name":"Centre for Cell Biology, Health Sciences Department and Biology Department, University of Aveiro, Aveiro, Portugal"}]},{"given":"Margarida","family":"Fardilha","sequence":"additional","affiliation":[{"name":"Centre for Cell Biology, Health Sciences Department and Biology Department, University of Aveiro, Aveiro, Portugal"}]},{"given":"Hideo","family":"Nishitani","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science, University of Hyogo, Hyogo, Japan"}]},{"given":"Roger M.","family":"Nitsch","sequence":"additional","affiliation":[{"name":"Division of Psychiatry Research, University of Zurich, Zurich, Switzerland"}]},{"given":"Edgar F.","family":"da Cruz e Silva","sequence":"additional","affiliation":[{"name":"Centre for Cell Biology, Health Sciences Department and Biology Department, University of Aveiro, Aveiro, Portugal"}]},{"given":"Odete A.B.","family":"da Cruz e Silva","sequence":"additional","affiliation":[{"name":"Centre for Cell Biology, Health Sciences Department and Biology Department, University of Aveiro, Aveiro, Portugal"}]}],"member":"179","published-online":{"date-parts":[[2014,10,10]]},"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-132495","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-132495","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:00:51Z","timestamp":1777370451000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-132495"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,10]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,10,10]]}},"alternative-id":["10.3233\/JAD-132495"],"URL":"https:\/\/doi.org\/10.3233\/jad-132495","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,10]]}}}