Zhang Y, Feng X H, Derynck R
Department of Growth and Development, Program in Cell Biology, University of California at San Francisco, 94143-0640, USA.
Nature. 1998 Aug 27;394(6696):909-13. doi: 10.1038/29814.
Smad proteins transduce signals for transforming growth factor-beta (TGF-beta)-related factors. Smad proteins activated by receptors for TGF-beta form complexes with Smad4. These complexes are translocated into the nucleus and regulate ligand-induced gene transcription. 12-O-tetradecanoyl-13-acetate (TPA)-responsive gene promoter elements (TREs) are involved in the transcriptional responses of several genes to TGF-beta (refs 5-8). AP-1 transcription factors, composed of c-Jun and c-Fos, bind to and direct transcription from TREs, which are therefore known as AP1-binding sites. Here we show that Smad3 interacts directly with the TRE and that Smad3 and Smad4 can activate TGF-beta-inducible transcription from the TRE in the absence of c-Jun and c-Fos. Smad3 and Smad4 also act together with c-Jun and c-Fos to activate transcription in response to TGF-beta, through a TGF-beta-inducible association of c-Jun with Smad3 and an interaction of Smad3 and c-Fos. These interactions complement interactions between c-Jun and c-Fos, and between Smad3 and Smad4. This mechanism of transcriptional activation by TGF-beta, through functional and physical interactions between Smad3-Smad4 and c-Jun-c-Fos, shows that Smad signalling and MAPK/JNK signalling converge at AP1-binding promoter sites.
Smad蛋白转导转化生长因子-β（TGF-β）相关因子的信号。被TGF-β受体激活的Smad蛋白与Smad4形成复合物。这些复合物被转运到细胞核中并调节配体诱导的基因转录。12-O-十四烷酰-13-乙酸酯（TPA）反应基因启动子元件（TREs）参与了几个基因对TGF-β的转录反应（参考文献5-8）。由c-Jun和c-Fos组成的AP-1转录因子与TREs结合并指导其转录，因此TREs被称为AP1结合位点。在这里，我们表明Smad3直接与TRE相互作用，并且在没有c-Jun和c-Fos的情况下，Smad3和Smad4可以激活来自TRE的TGF-β诱导转录。Smad3和Smad4还与c-Jun和c-Fos一起作用，通过c-Jun与Smad3的TGF-β诱导结合以及Smad3和c-Fos的相互作用来激活对TGF-β的转录反应。这些相互作用补充了c-Jun和c-Fos之间以及Smad3和Smad4之间的相互作用。TGF-β通过Smad3-Smad4与c-Jun-c-Fos之间的功能和物理相互作用进行转录激活的这种机制表明，Smad信号传导和MAPK/JNK信号传导在AP1结合启动子位点汇聚。
