After phosphorylated SMAD2/3 accumulate in the nucleus in response to TGF-beta stimulation, E3 ubiqutin ligases RNF111 (Arkadia) (Levy et al. 2007) and SMURF2 (Bonni et al. 2001) bind SKI/SKIL in complex with SMAD2/3:SMAD4 heterotrimer. The role of RNF111 was inferred from experiments that used recombinant mouse RNF111 and endogenous human SMADs and SKI/SKIL (Levy et al. 2007). The role of SMURF2 was inferred from experiments involving human proteins only (Bonni et al. 2001).