Briones-Orta Marco A, Sosa-Garrocho Marcela, Moreno-Alvarez Paola, Fonseca-Sánchez Miguel A, Macías-Silva Marina
Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D.F. 04510, Mexico.
Biochem Biophys Res Commun. 2006 Mar 17;341(3):889-94. doi: 10.1016/j.bbrc.2006.01.041. Epub 2006 Jan 23.
SnoN and Ski oncoproteins are co-repressors for Smad proteins and repress TGF-beta-responsive gene expression. The smad7 gene is a TGF-beta target induced by Smad signaling, and its promoter contains the Smad-binding element (SBE) required for a positive regulation by the TGF-beta/Smad pathway. SnoN and Ski co-repressors also bind SBE but regulate negatively smad7 gene. Ski along with Smad4 binds and represses the smad7 promoter, whereas the repression mechanism by SnoN is not clear. Ski and SnoN overexpression inhibits smad7 reporter expression induced through TGF-beta signaling. Using chromatin immunoprecipitation assays, we found that SnoN binds smad7 promoter at the basal condition, whereas after a short TGF-beta treatment for 15-30 min SnoN is downregulated and no longer bound smad7 promoter. Interestingly, after a prolonged TGF-beta treatment SnoN is upregulated and returns to its position on the smad7 promoter, functioning probably as a negative feedback control. Thus, SnoN also seems to regulate negatively the TGF-beta-responsive smad7 gene by binding and repressing its promoter in a similar way to Ski.
SnoN和Ski癌蛋白是Smad蛋白的共抑制因子，可抑制转化生长因子β（TGF-β）应答基因的表达。Smad7基因是由Smad信号诱导的TGF-β靶基因，其启动子含有TGF-β/Smad途径正向调控所需的Smad结合元件（SBE）。SnoN和Ski共抑制因子也结合SBE，但对Smad7基因起负调控作用。Ski与Smad4结合并抑制Smad7启动子，而SnoN的抑制机制尚不清楚。Ski和SnoN的过表达抑制通过TGF-β信号诱导的Smad7报告基因表达。通过染色质免疫沉淀分析，我们发现SnoN在基础条件下结合Smad7启动子，而在短时间（15 - 30分钟）的TGF-β处理后，SnoN被下调，不再结合Smad7启动子。有趣的是，在长时间的TGF-β处理后，SnoN上调并回到其在Smad7启动子上的位置，可能起负反馈调控作用。因此，SnoN似乎也通过与Ski类似的方式结合并抑制Smad7启动子，对TGF-β应答的Smad7基因起负调控作用。
