Deconjugating enzymes (DCEs) are proteases that process ubiquitin or ubiquitin-like gene products, reverse the modification of proteins by a single ubiquitin or ubiquitin-like protein (UBL) and remodel polyubiquitin (or poly-UBL) chains on target proteins (Reyes-Turcu et al., 2009). The deubiquitylating - or deubiquitinating - enzymes (DUBs) represent the largest family of DCEs and regulate ubiquitin dependent signalling pathways. The activities of the DUBs include the generation of free ubiquitin from precursor molecules, the recycling of ubiquitin following substrate degradation to maintain cellular ubiquitin homeostasis and the removal of ubiquitin or ubiquitin-like proteins (UBL) modifications through chain editing to rescue proteins from proteasomal degradation or to influence cell signalling events (Komander et al., 2009). There are two main classes of DUB, cysteine proteases and metalloproteases. Ubiquitin specific protease 21 (USP21) is a member of the cysteine protease enzyme family and cloning of the gene was first described by Gong et al. (2000). USP21 cleaves ubiquitin polymers, and with reduced activity also targets the UBL ISG15 but not NEDD8 (Ye et al., 2011). USP21 has been shown to be involved in the regulation of transcriptional initiation through the deubiquitylation of histone H2A as well as playing a role in the regulation of tumour necrosis factor α (TNFα) induced nuclear factor κβ (NF-κβ) activation by deubiquitylating receptor-interacting protein 1 (RIP1) (Nakagawa et al., 2008; Xu et al., 2010). Proteomic analyses also identified microtubule affinity-regulating (MARK) protein kinases and phosphatases as USP21 interactors, suggesting roles for USP21 in cell signalling (Li et al., 2005). In a recent screen of 66 DUBs tagged with green fluorescent protein (GFP), USP21 was found to be unique by showing clear association with both centrosomes and microtubules (Urbe et al., 2012).
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Urbe S, Liu H, Hayes SD, Heride C, Rigden DJ and Clague MJ (2012) Systematic survey of deubiquitinase localization identifies USP21 as a regulator of centrosome- and microtubule-associated functions. Molecular biology of the cell, 23, 1095-1103.
Xu G, Tan X, Wang H, Sun W, Shi Y, Burlingame S, et al. (2010) Ubiquitin-specific peptidase 21 inhibits tumor necrosis factor alpha-induced nuclear factor kappaB activation via binding to and deubiquitinating receptor-interacting protein 1. The Journal of biological chemistry, 285, 969-978.
Ye Y, Akutsu M, Reyes-Turcu F, Enchev RI, Wilkinson KD and Komander D (2011) Polyubiquitin binding and cross-reactivity in the USP domain deubiquitinase USP21. EMBO reports, 12, 350-357.