Abstract
Ubiquitin specific peptidase 2 (USP2) is a deubiquitinating enzyme expressed almost ubiquitously in the body, including in multiple brain regions. We previously showed that mice lacking USP2 present altered locomotor activity rhythms and response of the clock to light. However, the possible implication of USP2 in regulating other behaviors has yet to be tested. To address this, we ran a battery of behavioral tests on Usp2 KO mice. Firstly, we confirmed our prior findings of increased daily activity and reduced activity fragmentation in Usp2 KO mice. Further, mice lacking USP2 showed impaired motor coordination and equilibrium, a decrease in anxiety-like behavior, a deficit in working memory and in sensorimotor gating. On the other hand, no effects of Usp2 gene deletion were found on spatial memory. Hence, our data uncover the implication of USP2 in different behaviors and expands the range of the known functions of this deubiquitinase.
Highlights
Ubiquitination is the process of covalent attachment of a 76 kDa long protein called Ubiquitin to other proteins
We present evidence for a role of the deubiquitinating enzyme Ubiquitin specific peptidase 2 (USP2) in the central nervous system
In 2004, Graner and colleagues showed that USP2 binds to and stabilizes fatty acid synthase protein (FAS) [39], a protein known to be upregulated in many cancers including prostate cancer [40]
Summary
Ubiquitination is the process of covalent attachment of a 76 kDa long protein called Ubiquitin to other proteins. While ubiquitination has multiple roles in the functioning of the cell, including protein localization and trafficking [1], its most salient function is the targeting of tagged proteins for degradation [2]. The process of ubiquitination is counteracted by the process of deubiquitination, which is mediated by enzymes known as deubiquitinases or DUBs. The process of ubiquitination is counteracted by the process of deubiquitination, which is mediated by enzymes known as deubiquitinases or DUBs These opposing processes can, in essence, determine the timing of various processes such as degradation, activity and localization of proteins. While various DUBs are found in different tissues and cell types, Ubiquitin Specific Peptidase 2 or USP2 is one of the DUBs that has been found to be expressed almost ubiquitously in the organism [4,5,6,7]. It is the only DUB that has been found to have a circadian pattern of expression in virtually all the tissues where it is expressed [7, 8]
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