SMAD2 and neoplasm: In yet another study on breast cancer, the tumor suppressor function of the ubiquitin ligase PHRF1 was identified to occur through a ubiquitin-mediated decay of the homeodomain protein TGIF [304], a suppressor of the canonical TGF-β signaling pathway that directly represses cPML’s ability to enable SARA-dependent transport of Smad2 to TβRI (Figure 3).