The ubiquitin-mediated protein degradation pathway exerts a wide spectrum of
effects and modulates a variety of biological processes including cell cycle progression,
transcriptional regulation, signal transduction, antigen presentation, apoptosis (or
programmed cell death), oncogenesis, preimplantation, neuron degeneration, and DNA
damage repair. Recently, the importance of deubiquitination mechanism has been emerged as
an essential regulatory step to control these cellular mechanisms for homeostasis. As a
number of deubiquitinating enzymes have recently been isolated and characterized, their
substrates and biological functions have been illustrated. Identified from yeast to human,
deubiquitinating (DUB) enzymes are classified into the ubiquitin C-terminal hydrolase
(UCH), the ubiquitin-specific processing proteases (UBP or USP), Jab1/Pad1/MPN domain
containing metallo-enzymes (JAMM), Otu domain ubiquitin-aldehyde binding proteins
(OTU), and Ataxin-3/Josephin domain containing proteins (Ataxin-3/Josephin). Several
members of a novel DUB subfamily induced by cytokines in murine lymphocytes have
recently been identified. In addition, human DUB enzyme DUB-3, highly homologous to
USP17 and induced by cytokines interleukin (IL)-4 and IL-6, has been recently isolated and
showed that it has significant homology to the known murine DUB subfamily members.
Interestingly, both murine DUB and human USP17 subfamily members are localized and
clustered on murine chromosome 7 and on human chromosomes 4 and 8, respectively. This
review introduces the reader to provide a great understanding of cytokine-inducible DUB
enzymes in both mouse and human and new insights into DUB subfamily members.
Keywords: Cysteine protease, cytokine, deubiquitination, deubiquitomics, DUB
enzyme, E1 ubiquitin activating enzyme, E2 ubiquitin conjugating enzyme, E3
ubiquitin ligase, enhancer element, ERK, interleukin, JAK, JAMM, lymphocyte,
OTU, signaling, STAT, ubiquitin, ubiquitination, ubiquitin specific protease,
ubiquitomics, UCH.