The Role Of SUMO-specific Protease 1(senp1) In Adipogenesis

Obesity has been an increasingly serious health problem throughout the world which is always along with more serious metabolic-related disorders such as heart disease, diabetes, high blood pressure and even cancer. The disorder of adipogenesis has been linked to obesity. Adipogenesis is regulated by a transcriptional cascade, which mainly includes CCAAT/enhancer-binding protein(C/EBP) family members(i.e. C/EBPα, C/EBPβ, and C/EBPδ), the nuclear receptor peroxisome proliferator-activated receptor γ(PPARγ). This transcriptional cascade directs the extensive reprogramming of gene expression required to convert preadipocytes to mature adipocytes. Furthermore, it is well documented that post-translational modification plays a crucial role in adipogenesis.SUMOylation is one of post-translational modification. SUMO modification is a dynamic process catalyzed by E1, E2, and E3 and reversed by Sentrin/SUMO-specific proteases(SENPs). 6 SENP members have been identified in mammals, each of which has different cell localization and target specificity. Our previous data demonstrated that SENP1 plays a role in development. In this study, we used Senp1-/- MEF cells to determine the role of SENP1 in adipogenesis. We show the defects in adipocyte differentiation as well as PPARγ expression in Senp1-/- MEF cells induced by adipogenic stimuli. We further determine that SENP1 is a specific de-SUMOylation protease for Sharp-1, a repressor for PPARγ transcription and adipogenesis. SENP1 enhances adipogenesis through de-SUMOylation of Sharp-1, which then releases Sharp-1 repression of PPARγ expression and adipocyte differentiation. These results reveal SENP1 as a novel regulator in adipogenesis.