Effect Of TRiC/CCT Complex On Stability And Function Of WDTC1

In recent years,the incidence of metabolic diseases which caused by obesity has been increasing worldwidely.Obesity has been a hot research topic in the field of metabolism.Dysfunction of adipocytes is one of the main causes of obesity,but the metabolic process of adipocytes is complicated;therefore,researches on the anti-obesity genes will provide a new direction for solving the problems of obesity.WDTC1 encodes an evolutionarily conserved suppressor of lipid accumulation,is the ortholog gene of Adp.The study shows that heterozygous WDTC1 knockout mice displayed obesity,and WDTC1 play the same role in human.TRiC/CCT is a kind of primary eukaryotic cytosolic chaperonin,which is necessary for cytosolic protein folding and assembly,and thus prevents misfolding and aggregation during protein synthesis.The existence of TRiC/CCT is of great significance in order to keep proper functions of proteins.Some studies show that WDR68,which has a similar structure with WDTC1,was identified as a major binding protein of TRiC/CCT.Functioning as a molecular chaperone,TRiC/CCT is essential for correct protein folding and nuclear accumulation of WDR68.Accordingly,a series of experiments were carried out on the possible interaction between WDTC1 and TRiC/CCT.In this study,we have isolated cellular WDTC1 binding partners and identified TRiC/CCT is the major binding protein of WDTC1.Experiments with a series of deletion mutants show that the ADP domain of WDTC1 is key for its binding with CCT1 and CCT5 units of TRiC/CCT.We demonstrate that the molecular TRiC/CCT is essential for correct WDTC1 folding and the inhibitory effect of WDTC1 on adipogenesis.A study on the interaction between WDTC1 and TRiC/CCT were presented in this project.We identify that TRiC/CCT is essential for folding and function of WDTC1.These results provided the theoretical and experimental bases for further research on the function of anti-obesity gene.