TGFB1 and osteosarcoma: Additionally, the direct binding of E3 ligases Smad ubiquitination-related factor 1 (Smurf2) with E3 ubiquitin ligase RLIM (RING finger LIM domain-binding protein) markedly enhances the response of osteosarcoma U2OS cells to TGF-β (transforming growth factor-β) [68].