IRS1 and hepatocellular carcinoma: For instance, TRIM72 directly interacts with Ras-related C3 botulinum toxin substrate 1 (RAC1) through its coiled-coil domain and suppresses RAC1 activity by catalyzing the Lys48 (K48)-linked polyubiquitination of RAC1 at Lys5 residue in HCC cells [23]; Additionally, TRIM72 induces ubiquitination of insulin receptor substrate 1 (IRS-1) with the assistant of an E2-conjugating enzyme UBE2H [24, 25].