Zawel L, Dai J L, Buckhaults P, Zhou S, Kinzler K W, Vogelstein B, Kern S E
Molecular Genetics Laboratory, Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
Mol Cell. 1998 Mar;1(4):611-7. doi: 10.1016/s1097-2765(00)80061-1.
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 sequences (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.
越来越多的证据表明，Smad蛋白是转化生长因子β（TGFβ）信号传导所必需的，但Smad蛋白传递该信号的方式尚不清楚。我们发现，两种人类Smad蛋白（Smad3和Smad4）能够特异性识别相同的8碱基对回文序列（GTCTAGAC）。该回文序列的串联重复赋予了一个最小启动子显著的TGFβ反应性。通过靶向缺失细胞内的Smad4基因，这种反应性被消除。这些结果定义了Smad蛋白的一种新的生化特性，这可能在对TGFβ及相关配体的生物学反应中发挥直接作用。
