PMID- 36331254
OWN - NLM
STAT- MEDLINE
DCOM- 20221223
LR  - 20221223
IS  - 1347-6947 (Electronic)
IS  - 0916-8451 (Linking)
VI  - 87
IP  - 1
DP  - 2022 Dec 21
TI  - Ca2+/Calmodulin induces translocation of membrane-associated TSC2 to the nucleus 
      where it suppresses CYP24A1 expression.
PG  - 45-53
LID - 10.1093/bbb/zbac174 [doi]
AB  - 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.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of Japan 
      Society for Bioscience, Biotechnology, and Agrochemistry.
FAU - Kazami, Machiko
AU  - Kazami M
AUID- ORCID: 0000-0002-2477-8269
AD  - Department of Agricultural Chemistry, Faculty of Applied Bioscience, Tokyo 
      University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, Japan.
FAU - Sakamoto, Tomoya
AU  - Sakamoto T
AD  - Department of Agricultural Chemistry, Faculty of Applied Bioscience, Tokyo 
      University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, Japan.
FAU - Suzuki, Tsukasa
AU  - Suzuki T
AD  - Department of Agricultural Chemistry, Faculty of Applied Bioscience, Tokyo 
      University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, Japan.
FAU - Inoue, Hirofumi
AU  - Inoue H
AD  - Department of Agricultural Chemistry, Faculty of Applied Bioscience, Tokyo 
      University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, Japan.
FAU - Kato, Hayato
AU  - Kato H
AD  - Department of Agricultural Chemistry, Faculty of Applied Bioscience, Tokyo 
      University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, Japan.
FAU - Kobayashi, Ken-Ichi
AU  - Kobayashi KI
AD  - Department of Agricultural Chemistry, Faculty of Applied Bioscience, Tokyo 
      University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, Japan.
FAU - Tadokoro, Tadahiro
AU  - Tadokoro T
AD  - Department of Agricultural Chemistry, Faculty of Applied Bioscience, Tokyo 
      University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, Japan.
FAU - Yamamoto, Yuji
AU  - Yamamoto Y
AD  - Department of Agricultural Chemistry, Faculty of Applied Bioscience, Tokyo 
      University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, Japan.
LA  - eng
GR  - Vehicle Racing Commemorative Foundation/
PT  - Journal Article
PL  - England
TA  - Biosci Biotechnol Biochem
JT  - Bioscience, biotechnology, and biochemistry
JID - 9205717
RN  - 0 (Calmodulin)
RN  - EC 1.14.15.16 (Vitamin D3 24-Hydroxylase)
RN  - SY7Q814VUP (Calcium)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 1.14.15.16 (CYP24A1 protein, human)
RN  - Tuberous Sclerosis 2
SB  - IM
MH  - Rats
MH  - Humans
MH  - Animals
MH  - *Calmodulin/metabolism
MH  - Vitamin D3 24-Hydroxylase/metabolism
MH  - Calcium/metabolism
MH  - *Tuberous Sclerosis
MH  - HeLa Cells
MH  - Tuberous Sclerosis Complex 2 Protein/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - CYP24A1
OT  - CaM
OT  - TSC2
OT  - translocation
OT  - vitamin D metabolism
EDAT- 2022/11/05 06:00
MHDA- 2022/12/24 06:00
CRDT- 2022/11/04 09:32
PHST- 2022/07/11 00:00 [received]
PHST- 2022/10/31 00:00 [accepted]
PHST- 2022/11/05 06:00 [pubmed]
PHST- 2022/12/24 06:00 [medline]
PHST- 2022/11/04 09:32 [entrez]
AID - 6798381 [pii]
AID - 10.1093/bbb/zbac174 [doi]
PST - ppublish
SO  - Biosci Biotechnol Biochem. 2022 Dec 21;87(1):45-53. doi: 10.1093/bbb/zbac174.