@article{064935a4c94740e2a688c317f3fd67e6,
title = "Vitamin D Metabolite, 25-Hydroxyvitamin D, Regulates Lipid Metabolism by Inducing Degradation of SREBP/SCAP",
abstract = "Sterol regulatory element-binding proteins (SREBPs) are transcription factors that control lipid homeostasis. SREBP activation is regulated by a negative feedback loop in which sterols bind to SREBP cleavage-activating protein (SCAP), an escort protein essential for SREBP activation, or to insulin-induced genes (Insigs) (endoplasmic reticulum [ER] anchor proteins), sequestering the SREBP-SCAP-Insig complex in the ER. We screened a chemical library of endogenous molecules and identified 25-hydroxyvitamin D (25OHD) as an inhibitor of SREBP activation. Unlike sterols and other SREBP inhibitors, 25OHD impairs SREBP activation by inducing proteolytic processing and ubiquitin-mediated degradation of SCAP, thereby decreasing SREBP levels independently of the vitamin D receptor. Vitamin D supplementation has been proposed to reduce the risk of metabolic diseases, but the mechanisms are unknown. The present results suggest a previously unrecognized molecular mechanism of vitamin D-mediated lipid control that might be useful in the treatment of metabolic diseases.",
keywords = "SREBP, Vitamin D",
author = "Lisa Asano and Mizuki Watanabe and Yuta Ryoden and Kousuke Usuda and Takuya Yamaguchi and Bilon Khambu and Megumi Takashima and Sato, {Shin ichi} and Juro Sakai and Kazuo Nagasawa and Motonari Uesugi",
note = "Funding Information: We thank J. Iwata for technical assistance and K. Mori (Kyoto University) for providing an antibody. This work was supported in part by JSPS ( 26220206 to M.U.; 24710260 and 26350972 to M.W.), AMED-CREST (to M.U. and K.N.), P-DIRECT, AMED (to M.U. and K.N.), and the Collaborative Research Program of Institute for Chemical Research, Kyoto University (grant no. 83). L.A. is a JSPS predoctoral fellow (14J12469). iCeMS is supported by the World Premier International Research Center Initiative (WPI), MEXT, Japan. This work was inspired by the international and interdisciplinary environments of the iCeMS and JSPS Asian CORE Program, “Asian Chemical Biology Initiative.” M.U. has interests in FGH Biotech, Inc., a Houston-based company that exclusively licensed the technology described in this article. Funding Information: We thank J. Iwata for technical assistance and K. Mori (Kyoto University) for providing an antibody. This work was supported in part by JSPS (26220206 to M.U.; 24710260 and 26350972 to M.W.), AMED-CREST (to M.U. and K.N.), P-DIRECT, AMED (to M.U. and K.N.), and the Collaborative Research Program of Institute for Chemical Research, Kyoto University (grant no. 83). L.A. is a JSPS predoctoral fellow (14J12469). iCeMS is supported by the World Premier International Research Center Initiative (WPI), MEXT, Japan. This work was inspired by the international and interdisciplinary environments of the iCeMS and JSPS Asian CORE Program, ?Asian Chemical Biology Initiative.? M.U. has interests in FGH Biotech, Inc., a Houston-based company that exclusively licensed the technology described in this article. Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",
year = "2017",
month = feb,
day = "16",
doi = "10.1016/j.chembiol.2016.12.017",
language = "English",
volume = "24",
pages = "207--217",
journal = "Cell Chemical Biology",
issn = "2451-9448",
publisher = "Elsevier Inc.",
number = "2",
}