Cdh1 regulates osteoblast function through an APC/C-independent modulation of Smurf1.
Cdh1 regulates osteoblast function through an APC/C-independent modulation of Smurf1.
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DOI：
10.1016/j.molcel.2011.09.024
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发表时间：
2011-12-09
期刊：
影响因子：
16
通讯作者：
Wei W
中科院分区：
文献类型：
--
作者：
Wan L;Zou W;Gao D;Inuzuka H;Fukushima H;Berg AH;Drapp R;Shaik S;Hu D;Lester C;Eguren M;Malumbres M;Glimcher LH;Wei W
The APC/Cdh1 E3 ubiquitin ligase plays an essential role in both mitotic exit and G1/S transition by targeting key cell cycle regulators for destruction. There is mounting evidence indicating that Cdh1 has other functions in addition to cell cycle regulation. However, it remains unclear whether these additional functions depend on its E3 ligase activity. Here we report that Cdh1, but not Cdc20, promotes the E3 ligase activity of Smurf1. This is mediated by disruption of an auto-inhibitory Smurf1 homodimer and is independent of APC/Cdh1 E3 ligase activity. As a result, depletion of Cdh1 leads to reduced Smurf1 activity and subsequent activation of multiple downstream targets including the MEKK2 signaling pathway, inducing osteoblast differentiation. Our studies uncover a cell cycle-independent function of Cdh1, establishing Cdh1 as an upstream component that governs Smurf1 activity. They further suggest that modulation of Cdh1 is a potential therapeutic option for treatment of osteoporosis.
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影响因子：
50.3
作者：
Barbash, Olena;Zamfirova, Petia;Lin, Douglas I.;Chen, Xiangmei;Yang, Ke;Nakagawa, Hiroshi;Lu, Fengmin;Rustgi, Anil K.;Diehl, J. Alan
通讯作者：
Diehl, J. Alan
DOI：
10.1083/jcb.200309035
发表时间：
2004-01-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lindon C;Pines J
通讯作者：
Pines J
影响因子：
56.9
作者：
Konishi, Y;Stegm端ller, J;Bonni, A
通讯作者：
Bonni, A
影响因子：
64.5
作者：
KING, RW;PETERS, JM;KIRSCHNER, MW
通讯作者：
KIRSCHNER, MW
DOI：
10.1073/pnas.0510664103
发表时间：
2006-02-07
影响因子：
11.1
作者：
Gallagher, E;Gao, M;Karin, M
通讯作者：
Karin, M