Reactome: A Curated Pathway Database

SMAD2/3:SMAD4 heterotrimer forms a complex with RBL1, E2F4/5 and DP1/2 (R-HSA-2127257)

Species Homo sapiens


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).

Locations in the PathwayBrowser
Additional Information
Compartment nucleoplasm
Literature References
pubMedId Title Journal Year
12150994 E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression Cell 2002