Smad7 is inactivated through a direct physical interaction with the LIM protein Hic-5/ARA55.
Smad7 is inactivated through a direct physical interaction with the LIM protein Hic-5/ARA55.
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DOI：
10.1038/onc.2008.291
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发表时间：
2008-11-20
期刊：
影响因子：
8
通讯作者：
Danielpour, D.
中科院分区：
文献类型：
--
作者：
Wang, H.;Song, K.;Krebs, T. L.;Yang, J.;Danielpour, D.
We recently reported that hydrogen peroxide-inducible clone-5 (Hic-5, also named ARA55, androgen receptor-associated protein 55) can bind to the TGF-β signaling regulator Smad3, thereby inhibiting certain Smad3-dependent TGF-β responses. We now show that Hic-5 can also control TGF-β responses through an alternative mechanism involving Smad7, a key negative regulator of TGF-β signaling. Hic-5 binds directly to Smad7. This interaction requires the LIM3 domain of Hic-5, and enhances TGF-β signaling through causing loss of Smad7 protein but not mRNA. Enforced expression of Hic-5 reverses the ability of Smad7 to suppress TGF-β-induced phosphorylation of Smads 2 and 3 and activation of the plasminogen activator inhibitor-1 promoter (in NRP-154 and PC3 prostate carcinoma and WPMY-1 prostate myofibroblast cell lines). Lentiviral-mediated shRNA silencing of endogenous Hic-5 reduced TGF-β responses in PC3 and WPMY-1 cells. Further work suggests that the level of Smad7 is modulated by its physical interaction with Hic-5 and targeted to a degradation pathway not likely to be proteasomal. Our findings support that Hic-5 functions as a cell type-specific activator of TGF-β signaling through its ability to physically interact with and neutralize Smad7.
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影响因子：
4.8
作者：
Fujimoto, N;Yeh, SY;Chang, CS
通讯作者：
Chang, CS
影响因子：
4.8
作者：
Chipuk, JE;Cornelius, SC;Danielpour, D
通讯作者：
Danielpour, D
DOI：
10.1073/pnas.062010399
发表时间：
2002-03-19
影响因子：
11.1
作者：
Dong, CM;Zhu, SK;Goldschmidt-Clermont, PJ
通讯作者：
Goldschmidt-Clermont, PJ
影响因子：
4.8
作者：
Fujita, H;Kamiguchi, K;Tachibana, K
通讯作者：
Tachibana, K
影响因子：
9.2
作者：
Landström, M;Heldin, NE;Heldin, CH
通讯作者：
Heldin, CH