p-2S-SMAD2/3:SMAD4 p-2S-SMAD2/3:SMAD4 The SMAD2/3:SMAD4 complex transfers to the nucleus Authored: Heldin, CH, Moustakas, A, Huminiecki, L, Jassal, B, 2006-02-02 Edited: Jassal, B, 2006-02-10 14:02:35 Pubmed10934479 Pubmed11294908 Pubmed12592392 Pubmed16260601 Pubmed19114992 Pubmed20694664 Reactome Database ID Release 43173488 Reactome, http://www.reactome.org ReactomeREACT_6726 Reviewed: Chen, Ye-Guang, 2012-11-14 Reviewed: Heldin, CH, 2006-04-18 14:26:12 Reviewed: Huang, Tao, 2012-05-14 The phosphorylated R-SMAD:CO-SMAD complex rapidly translocates to the nucleus (Xu et al. 2000, Kurisaki et al. 2001, Xiao et al. 2003) where it binds directly to DNA and interacts with a plethora of transcription co-factors. Regulation of target gene expression can be either positive or negative. A classic example of a target gene of the pathway are the genes encoding for I-SMADs. Thus, TGF-beta/SMAD signaling induces the expression of the negative regulators of the pathway (negative feedback loop).