A new ubiquitin ligase involved in p57KIP2 proteolysis regulates osteoblast cell differentiation

被引：31

作者：

Kim, Minsoo ^{[1
]}

Nakamoto, Takashi ^{[1
]}

Nishimori, Shigeki ^{[1
]}

Tanaka, Keiji ^{[1
]}

Chiba, Tomoki ^{[1
,2
]}

机构：

[1] Tokyo Metropolitan Inst Med Sci, Core Technol & Res Ctr, Lab Frontier Sci, Bunkyo Ku, Tokyo 1138613, Japan

[2] Univ Tsukuba, Grad Sch Life & Environm Sci, Dept Mol Biol, Tsukuba, Ibaraki 3058572, Japan

来源：

EMBO REPORTS | 2008年 / 9卷 / 09期

关键词：

CDK inhibitor; F-box; osteoblast; TGF-beta; ubiquitin ligase;

D O I：

10.1038/embor.2008.125

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：

Transforming growth factor-beta 1 (TGF-beta 1) has many physiological functions and inhibits the differentiation of osteoblasts. Previously, we reported that TGF-beta 1 stimulation induces the degradation of p57(KIP2) in osteoblasts. p57(KIP2) proteolysis depends on the ubiquitin-proteasome pathway and SMAD-mediated transcription; however, the molecular mechanism underlying p57(KIP2) degradation has been largely unknown. Here, we show that FBL12, a new F-box protein expressed in the limb bud of developing embryos, is involved in TGF-beta 1-induced degradation of p57(KIP2). FBL12 formed an SCF(FBL12) complex and directly ubiquitinated p57(KIP2) in a phosphorylation-dependent manner. Inhibition of FBL12 by RNA interference suppressed the degradation of p57(KIP2) and a dominant-negative mutant of FBL12 (FBL12 Delta F) increased the steady-state level of p57(KIP2). Furthermore, wild-type FBL12 inhibited and FBL12DF promoted the differentiation of primary osteoblasts. As overexpression of p57(KIP2) promoted osteoblast differentiation, these results indicate the importance of FBL12 and the degradation of p57(KIP2) in the regulation of osteoblast cell differentiation.

引用

页码：878 / 884

页数：7

共 18 条

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