Identifying Novel Interaction Between SENP1 and the Deubiquitinating Enzyme Ubiquitin-Specific Protease 7 (USP7)

Abstract

Ubiquitin Specific Protease 7 (USP7) is a well-characterized deubiquitinating enzyme involved in numerous cellular pathways. Despite extensive studies, many USP7-regulated proteins and pathways remain unidentified. One emerging area of interest is the SUMOylation and deSUMOylation pathways, dynamic post-translational modifications increasingly recognized for their importance in protein regulation and disease progression. Through bioinformatics analysis, we identified SENP1, a deSUMOylating enzyme that contains a P/A/ExxS consensus motif, characteristic of known USP7 substrates. We hypothesized that USP7 interacts with and regulates SENP1, thereby modulating its stability and activity. Using various methods, including co-immunoprecipitation, silencing and overexpression in HCT116 cells, our findings demonstrate that USP7 interacts with and deubiquitinates SENP1, thus regulating its stability. Given SENP1’s involvement in various diseases, including cancer progression, and hypoxia signalling, our findings provide a novel insight into USP7-mediated regulation of deSUMOylation and highlights its potential as a therapeutic target.