SMAD4 and viral infectious disease: Additionally, two distinct research groups nearly concurrently discovered that mouse Smad4 suppresses viral infection and enhances the cytotoxicity of NK cells towards tumor cells, such as melanoma, with its regulatory mechanism being TGF-β independent, while the formation of a complex between Smad4 and JunB is synergistically enhance the transcription of GZMB (16, 19).