Function of Deubiquitinating Enzyme USP1 in Adipogenesis

Abstract

Obesity and metabolic disorders are one of the most challenging issues to be solved in modern society. Adipogenesis, which is a cellular differentiation process of pre-adipocyte to become a fully differentiated adipocyte, is a key mechanism in increasing fat mass and lipid accumulation. This process is a very complex multistep and involves numerous cascades of transcriptional factor activation. Accordingly, adipogenesis is regarded as a crucial target in treating or preventing obesity. Post-translational modification is a significant process for a protein to acquire its functional diversity in cell signaling by the addition or cleavage of functional groups. Deubiquitination by deubiquitinating enzyme is one of the important post-translational modifications involved in various signaling pathways. In this study, we screened deubiquitinating enzymes with differentiating 3T3-L1 adipocytes and found out that the mRNA and protein expression of ubiquitin specific peptidase 1 (USP1) was gradually increasing during the adipogenesis process. Also, from the various mouse tissue mRNA sample, ubiquitin specific peptidase 1 displayed higher expression levels on adipose tissues compared to other tissues. From these data, we assumed that this enzyme might be an important factor involved in adipogenesis. In the knockdown study, when ubiquitin specific peptidase 1 is absent, all the adipogenic transcription factors (Peroxisome proliferator-activated receptor gamma, Ccaat-enhancer-binding proteins alpha, beta, fatty acid synthase, and fatty acid binding protein 4) were down regulated. Furthermore, according to the proliferation assay result, ubiquitin specific peptidase 1 3T3-L1 cells had lower proliferation rate which indicates significant effect of USP1 during the mitotic clonal expansion. In consequence, our results indicate that ubiquitin specific peptidase 1 plays an important role in adipogenesis process. Disclosure J. Lee: None.