TGFBR1 and nonpapillary renal cell carcinoma: In-vitro studies, performed in ccRCC cell lines, also showed that the pVHL interacted with ALK5, indicating that pVHL thereby might regulate the protein stability of ALK5, consequently controlling the TGF-β signaling through proteasomal degradation of ALK5 by K48-linked poly-ubiquitination.