Negative regulation of BMP/Smad signaling by Tob in osteoblasts

被引：278

作者：

Yoshida, Y

Tanaka, S

Umemori, H

Minowa, O

Usui, M

Ikematsu, N

Hosoda, E

Imamura, T

Kuno, J

Yamashita, T

Miyazono, K

Noda, M

Noda, T

Yamamoto, T ^{[1
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Dept Oncol, Minato Ku, Tokyo 1088639, Japan

[2] Univ Tokyo, Fac Med, Dept Orthopaed Surg, Bunkyo Ku, Tokyo 113865, Japan

[3] Inst Canc Res, Dept Cell Biol, Toshima Ku, Tokyo 1708455, Japan

[4] Inst Canc Res, Dept Biochem, Toshima Ku, Tokyo 1708455, Japan

[5] Tokyo Med & Dent Univ, Inst Med Res, Dept Mol Pharmacol, Chiyoda Ku, Tokyo 1010062, Japan

来源：

CELL | 2000年 / 103卷 / 07期

基金：

日本学术振兴会;

关键词：

D O I：

10.1016/S0092-8674(00)00211-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Bone morphogenetic protein (BMP) controls osteoblast proliferation and differentiation through Smad proteins. Here we show that Tob, a member of the emerging family of antiproliferative proteins, is a negative regulator of BMP/Smad signaling in osteoblasts. Mice carrying a targeted deletion of the tob gene have a greater bone mass resulting from increased numbers of osteoblasts. Orthotopic bone formation in response to BMP2 is elevated in tob-deficient mice. Overproduction of Tob represses BMP2-induced, Smad-mediated transcriptional activation. Finally, Tob associates with receptor-regulated Smads (Smad1, 5, and 8) and colocalizes with these Smads in the nuclear bodies upon BMP2 stimulation. The results indicate that Tob negatively regulates osteoblast proliferation and differentiation by suppressing the activity of the receptor-regulated Smad proteins.

引用

页码：1085 / 1097

页数：13

共 42 条

[21] Characterization of a bone morphogenetic protein-responsive Smad-binding element [J].