TGFB1 and hereditary clear cell renal cell carcinoma: In the early stage, TGF‐β signaling is associated with favorable prognosis; while in the late stage, it correlates with poor prognosis, as the cancer cells metastasize to target organ sites.42 Loss of TGF‐β signaling has been shown in breast, prostate, and renal cell carcinoma.43, 44, 45 As mentioned above, SMURF2 restricts the TGF‐β signaling via monoubiquitination for blocking nuclear translocation of Smad complexes, as well as undergoing proteasomal degradation of Smads and TGF‐β receptors.