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- Title
Ca<sup>2+</sup>/Calmodulin induces translocation of membrane-associated TSC2 to the nucleus where it suppresses CYP24A1 expression.
- Authors
Machiko Kazami; Tomoya Sakamoto; Tsukasa Suzuki; Hirofumi Inoue; Hayato Kato; Ken-Ichi Kobayashi; Tadahiro Tadokoro; Yuji Yamamoto
- Abstract
Tuberous sclerosis complex 2 (TSC2) is a tumor-suppressor protein. 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.
- Subjects
CALMODULIN; VITAMIN D receptors; TUBEROUS sclerosis; GENETIC transcription regulation; VITAMIN D metabolism; CELLULAR signal transduction
- Publication
Bioscience, Biotechnology & Biochemistry, 2023, Vol 87, Issue 1, p45
- ISSN
0916-8451
- Publication type
Article
- DOI
10.1093/bbb/zbac174