Background
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 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 modifications through chain editing to rescue proteins from proteasomal degradation or to influence cell signaling events (Komander et al., 2009). There are two main classes of DUB; cysteine proteases and metalloproteases. Ubiquitin specific protease 36 (USP36) is a member of the cysteine protease enzyme family and cloning of the human gene was first described by Nagase et al. (2000). USP36 is primarily localized to the nucleoli, is required to maintain normal nucleolar structure and is highly expressed in skeletal muscle and testis. Nucleophosmin and fibrillarin are two nucleolar proteins that have been shown to undergo ubiquitylation, and are substrates for USP36. The deubiquitylating activity of USP36 controls transcriptional regulation and ribosome biogenesis in response to the changes in environmental conditions (Endo et al., 2009). USP36 is also known to deubiquitylate histone H2B and functions in gene silencing which is a common mechanism within stem cells in order to repress the premature expression of key differentiation genes, including Notch target genes (Buszczak et al., 2009). USP36 is overexpressed in ovarian cancer cells, and may act as an oncogene by suppressing differentiation (Li et al., 2008)
References
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Endo A, Matsumoto M, Inada T, Yamamoto A, Nakayama KI, Kitamura N, Komada M (2009) Nucleolar structure and function are regulated by the deubiquitylating enzyme USP36. J Cell Sci 122, 678-686.
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