Abstract
Small ubiquitin-like modifiers (SUMOs) become covalently conjugated to target proteins in a process called sumoylation. Desumoylation involves removal of the SUMO-moiety from target proteins. In higher eukaryotes, there are three related SUMO: SUMO-1, -2 & -3. Sumoylation modifies the physical properties and also the cellular functions of the target proteins. These modifications affect intracellular localization, protein-protein interactions, and other post-translational processes. These changes in turn modulate gene expression, genomic and chromosomal stability and integrity, and signal transduction. In humans, sumo-specific proteases (SENPs) are necessary for the sumoylation-desumoylation cycle. There are seven known human SENPs. SENPs are cysteine proteases which share a common catalytic mechanism: using a nucleophilic cysteine thiol in a catalytic triad to cleave peptide bonds within a protein. In this study, we focused on SENP1 and SUMO-1. Using a FRET-based SUMO processing assay, we screened for compounds that inhibited SENP1 from cleaving SUMO-1. Based on a computational algorithm, researchers from Yuan Chen?s lab selected 41 compounds to test. Eight of the compounds showed inhibition strength. By finding compounds that alter or inhibit SENP, it is possible to regulate the sumoylation-desumoylation process.
