Co-immunoprecipitation (Co-IP) and western blot assays indicated that transfection of D351H and R361H, two Smad4 constructs with mutation of the loop-helix region12, abolished the interaction of Smad4 with R-Smads, phosphorylated Smad1 and Smad2 (p-Smad1 and p-Smad2), in these NB cells (Supplementary Fig. S3c). This evidence concerns the gene SMAD1 and neuroblastoma.