Targeting the ubiquitin pathway for cancer treatment

• Ubiquitin ligases play a crucial role in the development and progression of cancer.
• Ubiquitin pathway components could be effective drug targets for cancer therapy.
• Bioactive compounds targeting ubiquitin pathway for cancer treatment are summarized.

Proteasome-mediated degradation is a common mechanism by which cells renew their intracellular proteins and maintain protein homeostasis. In this process, the E3 ubiquitin ligases are responsible for targeting specific substrates (proteins) for ubiquitin-mediated degradation. However, in cancer cells, the stability and the balance between oncoproteins and tumor suppressor proteins are disturbed in part due to deregulated proteasome-mediated degradation. This ultimately leads to either stabilization of oncoprotein(s) or increased degradation of tumor suppressor(s), contributing to tumorigenesis and cancer progression. Therefore, E3 ubiquitin ligases including the SCF types of ubiquitin ligases have recently evolved as promising therapeutic targets for the development of novel anti-cancer drugs. In this review, we highlighted the critical components along the ubiquitin pathway including E1, E2, various E3 enzymes and DUBs that could serve as potential drug targets and also described the available bioactive compounds that target the ubiquitin pathway to control various cancers.