Kang Yibin, Chen Chang-Rung, Massagué Joan
Cell Biology Program and Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Mol Cell. 2003 Apr;11(4):915-26. doi: 10.1016/s1097-2765(03)00109-6.
Genome-wide transcriptional profiling of human epithelial cells revealed that repression of Id inhibitors of differentiation (Id1, Id2, and Id3) is a general feature of the TGFbeta cytostatic program. Opposite responses of Id1 to TGFbeta and the related factor BMP are dictated by the specific ability of the TGFbeta mediator, Smad3, to activate expression of stress response factor ATF3 and then recruit this factor to the Id1 promoter. Thus, a Smad3-mediated primary gene response, ATF3 induction, enables Smad3 to participate in an ATF3-mediated, secondary gene response. As a common target of TGFbeta/Smad signals and stress signals via p38 kinase, ATF3 additionally serves to channel synergy between these pathways in the response of epithelial cells to stress and injury.
人类上皮细胞的全基因组转录谱分析表明，抑制分化抑制因子（Id1、Id2和Id3）是TGFβ细胞生长抑制程序的一个普遍特征。Id1对TGFβ和相关因子BMP的相反反应取决于TGFβ介质Smad3激活应激反应因子ATF3表达并随后将该因子招募至Id1启动子的特定能力。因此，Smad3介导的初级基因反应（ATF3诱导）使Smad3能够参与ATF3介导的次级基因反应。作为TGFβ/Smad信号和通过p38激酶的应激信号的共同靶点，ATF3还起到在这些途径之间传递协同作用的作用，以响应上皮细胞的应激和损伤。
