Functions of Ubiquitin Specific Proteases

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Eukaryotic cells rely on the ubiquitination of proteins for the proper control of their internal processes. Adding multiple ubiquitin groups aids in the breakdown of proteins, whereas adding only one ubiquitin serves regulatory roles other than degradation. The enzymatic activity of two protease classes frees ubiquitin groups from associated proteins: Ubiquitin specific proteases (USP) and Ubiquitin C-terminal hydrolases (UCH). USPs are strongly involved in eukaryotic cellular functions and are found in copious amounts. Certain protein ligases attach ubiquitin to proteins, which degrades them and interferes with normal cellular functions. The discovery of a specific de-ubiquitinating enzyme (HAUSP/USP7) found in humans was due to its association with a herpes ligase (ICP0). USP7 interacts with the ligase by binding to a site responsible for gene expression. USP7 interacts with the herpes protein EBNA1 as well, which associates with the proteins of the infected cell and controls regulation of viral genes when the herpes infection is in its dormant phase. In addition, USP7 is involved in the stabilization of the tumor suppressor p53, as found by a previous study (Li et al. 2002). USP7 over-expression induces programmed cell death (apoptosis) and simultaneously stabilizes p53 by releasing high amounts of the de-ubiquinated form. The USP7 interaction with both ICP0 and EBNA1 may affect cellular functioning by first manipulating the particular protease. This is researched in detail by examining the physical form of USP7 and finding the domains that interact with theses viral proteins and assessing the competition between p53 and EBNA1 for these sites of contact. The cDNA of the de-ubiquinating enzyme under study (USP7) was cut usin... ... middle of paper ... ...tant pathway for p53 stabilization and methods” by Li et al. which shed a light upon the stabilizing effect of USP7 binding to p53, and expanded on the USP7 structure and function. The results and findings were supported by experimental data, which were appropriate and resourceful for the study. The data was shown with clarity through an array of tables, graphs, and figures. Accordingly, the conclusions drawn were reasonable with respect to the results of the experimental tests. The findings prompted further research, as found by the study conducted in 2005 by Saridakis et al., which expanded on the structure of the specific domain that EBNA1 and p53 compete for. While the paper agreed with the range of amino acid resides involved in the binding site, it implied that specific residues are more involved than others (436-450 rather than the wider range of 395-450).

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