Published in: Science, vol. 283, no. 5406, pp. 1317-1321 (February 26, 1999):

Junn Yanagisawa¹, Yasuo Yanagi¹, Yoshikazu Masuhiro¹, Miyuki Suzawa^1,2, Michiko Watanabe¹, Kouji Kashiwagi¹, Takeshi Toriyabe¹, Masahiro Kawabata³, Kohei Miyazono³, and Shigeaki Kato^1,2.

¹Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.

²CREST, Japan Science and Technology, 4-1-8 Honcho, Kawaguchi, Saitama 332, Japan.

³Department of Biochemistry, The Cancer Institute, Tokyo, Japanese Foundation for Cancer Research (JFCR), and Research for the Future Program, Japan Society for the Promotion of Science, 1-37-1 Kami-Ilebukuro, Toshima-ku, Tokyo, 170-8455, Japan.

Abstract:

Cell proliferation and differentiation are regulated by growth regulatory factors such as transforming growth factor-Beta (TGF-Beta) and the lipophilic hormone vitamin D. TGF-Beta causes activation of SMAD proteins acting as coactivators or transcription factors in the nucleus. Vitamin D controls transcription of target genes through the vitamin D receptor (VDR). Smad3, one of the SMAS proteins downstream in the TGF-Beta signaling pathway, was found in mammalian cells to act as a coactivator specific for the ligand-induced transactivation of VDR by forming a complex with a member of the steroid receptor coactivator-1 protein family in the nucleus. Thus, Smad3 may mediate cross-talk between vitamin D and TGF-Beta signaling pathways.