SMAD4 and colorectal carcinoma: Further experimental data is needed to unravel the precise mechanisms underlying Smad activation by TRIM25. In contrast to TRIM25, TRIM47 induces CRC proliferation through negatively interfering with TGFβ-Smad-signaling by increasing ubiquitination and degradation of the Co-Smad protein Smad4 (Figure 3A) [119].