Ubiquitination is one of the most important post-translational modifications of proteins with a profound effect on their intracellular stability and activity. Deubiquitinases (DUBs), on the other hand, act by removing the ubiquitin moiety from proteins and thereby reverse their stability and/or activity. Besides, DUBs play a major role in maintenance of free ubiquitin pool, histone modification, vesicular trafficking and receptor recycling. The revelation of DUB interactome by Sowa et al.,  highlighted the importance of DUBs in key cellular pathways. While the role of E3 ubiquitin ligases in the virus biology is well documented, the involvement of DUBs in viral life cycle is still being probed. Recent findings suggest DUBs could play a central role in invasion and pathogenesis of oncogenic viruses. Viral oncoproteins such as E6 and E7 of human papilloma virus and Tax of human T-cell leukemia virus type 1 are now known to target cellular DUBs such as cyclindromatosis tumor suppressor, ubiquitin-specific proteases 7, 11, 15 and 20, A-20 and signal-transducing adaptor molecule binding protein-like-1 in order to improve their intracellular stability and/or subjugate cellular signaling pathways. The viral oncoprotein-DUB interactions create an ambience leading to unbridled proliferation of virus-infected cells and drive cell transformation. Interestingly, some viruses like herpes simplex virus-1, Epstein-Barr virus, human cytomegalovirus and Kaposi’s Sarcoma-associated herpes virus also encode their own DUBs such as UL36, UL48, BPLF1 and ORF64 to support viral invasion, replication, and persistence and even subvert host immune responses. Efforts are also underway to find specific inhibitors that can abrogate the interaction between cellular DUB and viral oncoproteins or inhibit viral DUBs as this might result in the development of next generation cancer chemotherapeutic agents. This review showcases the relevance of the viral DUBs and the cellular DUBs with interacting viral partners in virus-triggered cancer development.
Keywords: Deubiquitinase, interactome, oncogenic viruses, ubiquitination, ubiquitin proteasome system