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A loss of TSC2 function induces hyperactivation of mechanistic target of rapamycin (mTOR). The C-terminal region of TSC2 contains a calmodulin (CaM) binding region and the CaM-TSC2 interaction contributes to proper mTOR activity. However, other downstream signaling pathways\/effectors activated by the CaM-TSC2 complex have not been fully elucidated. In this study, we found that activation of Ca2+\/CaM signaling resulted in the translocation of membrane-associated TSC2 to the nucleus and suppressed the transcriptional activity of the vitamin D receptor (VDR). TSC2 was released from the membrane in an activated CaM-dependent state in rat brain and HeLa cells. It subsequently formed a transcriptional complex to partially suppress the transcription of CYP24A1, a well-known VDR target gene. These data suggest, in part, that TSC2 attenuates VDR-associated transcriptional regulation via Ca2+\/CaM signaling.<\/jats:p>","DOI":"10.1093\/bbb\/zbac174","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T17:47:22Z","timestamp":1667584042000},"page":"45-53","source":"Crossref","is-referenced-by-count":5,"title":["Ca2+\/Calmodulin induces translocation of membrane-associated TSC2 to the nucleus where it suppresses<i>CYP24A1<\/i>expression"],"prefix":"10.1093","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2477-8269","authenticated-orcid":false,"given":"Machiko","family":"Kazami","sequence":"first","affiliation":[{"name":"Department of Agricultural Chemistry, Faculty of Applied Bioscience, Tokyo University of Agriculture , 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoya","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of 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