Nuclear export of Smad2 and Smad3 by RanBP3 facilitates termination of TGF-beta signaling.
Nuclear export of Smad2 and Smad3 by RanBP3 facilitates termination of TGF-beta signaling.
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DOI：
10.1016/j.devcel.2009.01.022
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发表时间：
2009-03
影响因子：
11.8
通讯作者：
Feng, Xin-Hua
中科院分区：
文献类型：
--
作者：
Dai, Fangyan;Lin, Xia;Chang, Chenbei;Feng, Xin-Hua
Smad2和Smad3 （Smad2/3）是TGF-β信号传导的关键细胞内信号转导，其转录活性通过可逆磷酸化和核胞质穿梭控制。然而，Smad2/3核输出的确切机制仍然难以捉摸。本文报道了RanBP3在TGF-β通路Smad2/3选择性核输出中的重要作用。RanBP3直接识别核Smad磷酸酶活性导致的Smad2/3去磷酸化，并以ran依赖的方式介导Smad2/3的核输出。结果表明，RanBP3表达增加可抑制哺乳动物细胞和爪蟾胚胎中TGF-β信号传导。相反，RanBP3表达的缺失或RanBP3的显性负抑制会增强tgf β诱导的抗增殖和转录反应。总之，我们的研究支持RanBP3在介导Smad2/3核输出和终止TGF-β信号传导中的明确作用。
Smad2 and Smad3 (Smad2/3) are key intracellular signal transducers for TGF-β signaling and their transcriptional activities are controlled through reversible phosphorylation and nucleocytoplasmic shuttling. However, the precise mechanism underlying nuclear export of Smad2/3 remains elusive. Here we report the essential function of RanBP3 in selective nuclear export of Smad2/3 in the TGF-β pathway. RanBP3 directly recognizes dephosphorylated Smad2/3, which results from the activity of nuclear Smad phosphatases, and mediates nuclear export of Smad2/3 in a Ran-dependent manner. As a result, increased expression of RanBP3 inhibits TGF-β signaling in mammalian cells and Xenopus embryos. Conversely, depletion of RanBP3 expression or dominant negative inhibition of RanBP3 enhances TGFβ-induced anti-proliferative and transcriptional responses. In conclusion, our study supports a definitive role of RanBP3 in mediating Smad2/3 nuclear export and terminating TGF-β signaling.
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RanBP3 独立于 CRM1 增强活性 (β)-连环蛋白的核输出。
影响因子：
7.8
作者：
Hendriksen, J;Fagotto, F;van der Velde, H;van Schie, M;Noordermeer, J;Fornerod, M
通讯作者：
Fornerod, M
影响因子：
10.5
作者：
Feng, XH;Zhang, Y;Derynck, R
通讯作者：
Derynck, R
影响因子：
5.3
作者：
Schmierer, B;Hill, CS
通讯作者：
Hill, CS
DOI：
10.1385/1-59259-750-5:085
发表时间：
2004-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Cullen, Bryan R
通讯作者：
Cullen, Bryan R
影响因子：
16
作者：
Feng, XH;Liang, YY;Lin, X
通讯作者：
Lin, X