CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation.
CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation.
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CHIP 促进 Runx2 降解并负向调节成骨细胞分化
DOI：
10.1083/jcb.200711044
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发表时间：
2008-06-16
影响因子：
7.8
通讯作者：
Chang, Zhijie
中科院分区：
文献类型：
--
作者：
Li, Xueni;Huang, Mei;Zheng, Huiling;Wang, Yinyin;Ren, Fangli;Shang, Yu;Zhai, Yonggong;Irwin, David M.;Shi, Yuguang;Chen, Di;Chang, Zhijie
Runx2是成骨细胞分化的重要转录激活因子，在转录和翻译后水平均受到严格调控。本文中，我们报道了CHIP （hsc70相互作用蛋白C端）/STUB1通过泛素化降解机制调控Runx2蛋白的稳定性。CHIP在体外和体内与Runx2相互作用。在Runx2蛋白水平升高的情况下，CHIP表达降低，而其他参与Runx2降解的E3连接酶，如Smurf1或WWP1的表达在成骨细胞分化过程中保持不变或增加。CHIP的缺失导致Runx2的稳定，增强Runx2介导的转录激活，并促进原代颅骨细胞的成骨细胞分化。相反，CHIP在成骨前细胞中的过表达导致Runx2降解，抑制成骨细胞分化，反而促进脂肪形成。我们的数据表明，CHIP对Runx2蛋白的负调控在前体细胞向成骨细胞谱系分化的过程中至关重要。
Runx2, an essential transactivator for osteoblast differentiation, is tightly regulated at both the transcriptional and posttranslational levels. In this paper, we report that CHIP (C terminus of Hsc70-interacting protein)/STUB1 regulates Runx2 protein stability via a ubiquitination-degradation mechanism. CHIP interacts with Runx2 in vitro and in vivo. In the presence of increased Runx2 protein levels, CHIP expression decreases, whereas the expression of other E3 ligases involved in Runx2 degradation, such as Smurf1 or WWP1, remains constant or increases during osteoblast differentiation. Depletion of CHIP results in the stabilization of Runx2, enhances Runx2-mediated transcriptional activation, and promotes osteoblast differentiation in primary calvarial cells. In contrast, CHIP overexpression in preosteoblasts causes Runx2 degradation, inhibits osteoblast differentiation, and instead enhances adipogenesis. Our data suggest that negative regulation of the Runx2 protein by CHIP is critical in the commitment of precursor cells to differentiate into the osteoblast lineage.
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影响因子：
64.5
作者：
Hoppe, T;Cassata, G;Baumeister, R
通讯作者：
Baumeister, R
影响因子：
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作者：
Komori, T
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Komori, T
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影响因子：
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作者：
Ducy, P;Zhang, R;Karsenty, G
通讯作者：
Karsenty, G
影响因子：
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作者：
Hong, JH;Hwang, ES;Yaffe, MB
通讯作者：
Yaffe, MB
影响因子：
56.9
作者：
Jones, Dallas C.;Wein, Marc N.;Glimcher, Laurie H.
通讯作者：
Glimcher, Laurie H.