RBL1:E2F4/5:DP1/2 p-SMAD2/3:SMAD4:RBL1:E2F4/5:DP1/2 p-2S-SMAD2/3:SMAD4 SMAD2/3:SMAD4 heterotrimer forms a complex with RBL1, E2F4/5 and DP1/2 Authored: Orlic-Milacic, M, 2012-04-04 Edited: Jassal, B, 2012-04-10 In response to TGF-beta stimulation, a complex composed of SMAD2/3:SMAD4 heterotrimer and RBL1 (p107), E2F4/5 and DP1/2 can be detected in the nucleus. Formation of this complex was confirmed by both co-immunoprecipitation of the endogenous complex from the human keratinocyte cell line HaCat and by protein interaction studies using tagged recombinant proteins. It is possible that cells contain pre-assembled cytosolic complexes of SMAD2/3, RBL1 (p107) and E2F4/5, that translocate to the nucleus after TGF-beta stimulation, when phosphorylated SMAD2/3 recruit SMAD4. The MH2 domain of SMAD3 establishes independent contacts with the N-termini of E2F4 (or E2F5) and unphosphorylated RBL1 (p107). RBL2 (p130), RB1 and E2F1 do not interact with SMAD2/3 (Chen et al. 2002). Pubmed12150994 Reactome Database ID Release 432127257 Reactome, http://www.reactome.org ReactomeREACT_121097 Reviewed: Huang, Tao, 2012-05-14