The deubiquitylating enzymes (DUBs) regulate ubiquitin dependent signaling 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 protein (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 enzyme the cysteine proteases and metalloproteases. OTUB2 is a cysteine protease and member of the Ovarian Tumor (OTU) protein super family. Cloning of the human OTUB2 gene was first described by Balakirev et al., (2003). OTUB2 contains Ubiquitin Interaction Motifs (UIMs) and Ubiquitin Associated (UBA) domains, as well as putative nuclear localization signals and a consensus LxxLL motif (Balakirev et al., 2003). De-ubiquitylation has emerged as a post translational mechanism for the activation of virus triggered type I interferon (IFN) (2) induction pathways. OTUB2 has been found to negatively regulate virus triggered type I IFN activation of IRF3 and NF-kappaB by mediating the de-ubiquitylation of TRAF3 and TRAF6, two ubiquitin E3 ligases involved in virus-triggered IRF3 and NF-kappaB activation pathways (Li et al., 2010). Integrative gene tissue array analysis has been used to locate disease relevant proteins to a linkage region associated with familial Amyotrophic Lateral Sclerosis (ALS)/frontotemporal dementia. Using this approach OTUB2 was identified as a disease relevant protein involved in TAU-1 and SOD1 induced motor neuron degeneration found in human sporadic ALS (SALS) (Kudo et al., 2010).
Balakirev MY, Tcherniuk SO, Jaquinod M, Chroboczek J (2003) Otubains: a new
family of cysteine proteases in the ubiquitin pathway. EMBO Rep 4, 517-22.
Komander D, Clague MJ, Urbe S (2009) Breaking the chains: structure and function
of the deubiquitinases. Nat Rev Mol Cell Biol 10, 550-63.
Kudo LC, Parfenova L, Vi N, Lau K, Pomakian J, Valdmanis P, Rouleau GA, Vinters HV, Wiedau-Pazos M, Karsten S (2010) Integrative gene-tissue microarray-based approach for identification of human disease biomarkers: application to amyotrophic lateral sclerosis. Hum Mol Genet 19, 3233 - 3253.
Li S, Zheng H, Mao AP, Zhong B, Li Y, Liu Y, Gao Y, Ran Y, Tien P, Shu HB (2010) Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6. J Biol Chem 285, 4291-7.