Sumoylation of Smad4 at K159 promotes its interaction with the transcriptional corepressor Daxx to repress the transcriptional activity of Smad4, thereby inhibiting the TGF-β-Smad4 signaling pathway and playing the role of a tumor suppressor in breast cancer (Fig. 5C III) [150]. The gene discussed is TGFB1; the disease is breast carcinoma.