Molecular mechanisms and functions of cytokine-inducible deubiquitinating enzymes

Deubiquitinating enzymes (DUBs), a class of cysteine proteases which counteract the action of protein ubiquitination, hydrolyze ubiquitin from its specific targeted proteins. Approximately, 100 DUBs have been found from yeast to human, and they can be classified into at least 5 families based on their structures and functions. Most DUBs are involved in regulation of intracellular processes including cell cycle progression, apoptosis, immunity, reproduction, and target gene transcription. Recently, much progress has been made in understanding the physiological functions of cytokine-inducible DUBs such as DUB-1, DUB-2, and DUB-3/USP17, in regulation of cell proliferation and apoptosis in lymphocytes. Here, we have summarized the structure and functions of cytokine-inducible DUBs and their biological functions in regulating several interleukin-associated signaling pathways. Finally, we emphasize the importance of small molecules for cytokine-inducible DUBs for developing promising drug therapeutics for immune-related disorders.