Human Smad3 and Smad4 are sequence-specific transcription activators

Human Smad3 and Smad4 are sequence-specific transcription activators
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DOI:
10.1016/s1097-2765(00)80061-1
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发表时间:
1998-03-01
期刊:
影响因子:
16
通讯作者:
Kern, SE
Kern, SE
中科院分区:
生物学1区
文献类型:
--
作者:
Zawel, L;Dai, JL;Kern, SE

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越来越多的证据表明,Smad蛋白是TGF β信号传导所必需的,但Smad蛋白传播这种信号的方式尚不清楚。我们发现两个人Smad蛋白(Smad3和Smad4)可以特异性识别一个相同的8 bp回文序列(GTCTAGAC)。该回文序列的串联重复赋予对最小启动子的显著TGF β响应性。这种反应性被细胞Smad4基因的靶向缺失所消除。这些结果定义了Smad蛋白的一种新的生化特性,其可能在对TGF β和相关配体的生物反应中发挥直接作用。
Mounting evidence indicates that Smad proteins are required for TGF beta signaling, but the way(s) in which Smad proteins propagate this signal is unclear. We found that two human Smad proteins (Smad3 and smad4) could specifically recognize an identical 8 bp palindromic sequence (GTCTAGAC). Tandem repeats of this palindrome conferred striking TGF beta responsiveness to a minimal promoter. This responsiveness was abrogated by targeted deletion of the cellular Smad4 gene. These results define a novel biochemical property of Smad proteins that is likely to play a direct role in the biologic responses to TGF beta and related ligands.