p-2S-SMAD2/3:SMAD4:SKI/SKIL:NCOR p-2S-SMAD2/3:SMAD4 NCOR SKI/SKIL SKI/SKIL binds SMAD complex, suppressing TGF-beta signaling Authored: Heldin, CH, Moustakas, A, Huminiecki, L, Jassal, B, 2006-02-02 Edited: Jassal, B, 2006-02-10 14:02:35 Edited: Jassal, B, 2012-04-10 Pubmed10485843 Pubmed10531062 Pubmed10535941 Pubmed10549282 Pubmed11389444 Reactome Database ID Release 43173481 Reactome, http://www.reactome.org ReactomeREACT_6887 Reviewed: Heldin, CH, 2006-04-18 14:26:12 Reviewed: Huang, Tao, 2012-05-14 SKI and SKIL (SNO) are able to recruit NCOR and possibly other transcriptional repressors to SMAD2/3:SMAD4 complex, inhibiting SMAD2/3:SMAD4-mediated transcription (Sun et al. 1999, Luo et al. 1999, Strochein et al. 1999). Experimental findings suggest that SMAD2 and SMAD3 may target SKI and SKIL for degradation (Strochein et al. 1999, Sun et al. 1999 PNAS, Bonni et al. 2001), and that the ratio of SMAD2/3 and SKI/SKIL determines the outcome (inhibition of SMAD2/3:SMAD4-mediated transcription or degradation of SKI/SKIL). SKI and SKIL are overexpressed in various cancer types and their oncogenic effect is connected with their ability to inhibit signaling by TGF-beta receptor complex.