In contrast, itchy E3 ubiquitin-protein ligase (ITCH) and HECT domain and RCC1-like domain-containing protein 3 (HERC3) suppress CRC cell proliferation and lead to G0/G1 phase arrest by targeting at CDK4 and RPL23A for K48-linked ubiquitination degradation respectively [8, 9]. Here, HERC3 is linked to colorectal carcinoma.