Proteolysis Targeting Peptide(PROTAP) Strategy For Protein Ubiquitination And Degradation

Ubiquitination is an enzyme dependent cascade reaction,which is one of the most important highly specific posttranslational modifications in cell.It plays an extremely important role in the process of cell life,involving protein degradation,signal transduction,transcription regulation,cell cycle regulation,and so on.Ubiquitin-proteasome pathway is a hot issue in the study of ubiquitination,and the pathway has been an important target for disease research and drug development.Ubiquitin proteasome pathway is one of the most important protein specific degradation pathways in cells.Now,based on the high specificity of UPP scientists have developed many kinds of method to induce target protein degradation through the UPP in cells,which can remove the diseases related protein and ultimately achieve the purpose of disease treatment.These researches have become a hot field in the study of protein ubiquitination and have got lots of positive results.This research shows a novel proteolysis targeting peptide strategy,PROTAP,which based on the theory of interaction between protein and protein to induce polyubiquitination and degradation of the target protein through UPP.We have done many experiments so as to prove the effectiveness of PROTAP.Firstly,we demonstrated specific interaction between PROTAP and target protein by fluorescence polarization.Then,we simulated the environment of ubiquitination in cell and established the system in vitro to verify the effect of PROTAP in it.We got the prime concentration and time of PROTAP induces effect.Based on the all previous experiment results,we finally proved that the novel PROTAP is a effective and specific strategy to induce ubiquitination and degradation of target protein through UPP.PROTAP we designed is of high specificity and efficiency.If replace the target specific binding ligands,we can get a new PROTAP for corresponding target protein.In the future,we hope to improve the performance of PROTAP by chemical modification,and hope that it can be applied to the study of disease therapy.