Human Smad3 and Smad4 are sequence-specific transcription activators

被引:908
作者
Zawel, L
Dai, JL
Buckhaults, P
Zhou, SB
Kinzler, KW
Vogelstein, B [1 ]
Kern, SE
机构
[1] Johns Hopkins Oncol Ctr, Mol Genet Lab, Baltimore, MD 21231 USA
[2] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21208 USA
[3] Johns Hopkins Univ, Ctr Oncol, Baltimore, MD 21208 USA
[4] Howard Hughes Med Inst, Baltimore, MD 21231 USA
关键词
D O I
10.1016/S1097-2765(00)80061-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:611 / 617
页数:7
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