Proteasomal Deubiquitinase UCH37 Inhibits The Degradation Of ?-catenin And Promotes Cell Proliferation And Motility

Ubiquitin-proteasome system is currently a very important protein degradation pathway in eukaryotes.It involves in signal transduction,cell cycle regulation,apoptosis,DNA repair and transcriptional regulation.It is believed that the ubiquitin proteasome system can rapidly and accurately regulate the target protein by ubiquitinases and deubiquitinases.Ubiquitin carboxyl terminal hydrolase-5?UCH-L5?,also known as UCH37,is an important member of ubiquitin proteasome system.UCH37 is localized to proteasome and is the only member of ubiquitin carboxyl terminal hydrolase family that directly associated with proteasome.UCH37 gene knockdown in mammalian cells by CRISPR/cas9 technology,and we found the level of proteasome subunits,cell proliferation protein and transcriptional protein have changed.The?-catenin degradation was induced by different concentration of H₂O₂.It was found that the degradation of?-catenin was accelerated after knockout of UCH37 gene in mammalian cells.It suggests that?-catenin may directly act as a substrate of UCH37 for deubiquitination.Later,we found that UCH37 could mediate the binding of ubiquitin?Ub?to?-catenin so that reducing the level of ubiquitination of?-catenin.These results further indicate that?-catenin is a direct substrate of UCH37 for deubiquitination,in the meantime we found UCH37 plays functions of promoting cell mortality and cell proliferation by soft agar analysis and wound healing.