Ubiquitination is a crucial post-translational modification (PTM) of proteins and regulates their stabilities and activities, thereby modulating multiple signaling pathways. UbcH5c, a member of the UbcH5 ubiquitin-conjugating enzyme (E2) protein family, engages in the ubiquitination of dozens of proteins and regulates nuclear factor kappa-B (NF-κB), p53 tumor suppressor, and several other essential signaling pathways. UbcH5c has been reported to be abnormally expressed in human cancer and immune disorders and is involved in the initiation and progression of these diseases. In this review, we mainly focus on UbcH5c structure, activity, signaling pathways, and its relevance to cancer and immune disorders. We end by integrating all known factors relating to UbcH5c inhibition as a potential cancer therapy method, and discuss associated challenges.
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