The Molecular Mechanism And Function Of Crotonylation Modification Of CDK1

Cell proliferation is the most important feature in the life activities of biological cells.The process of cell proliferation is also called the cell cycle.It refers to the process from the end of one division to the end of the next division.The cell cycle is a delicate process that requires the joint regulation of various factors inside and outside.Among them,the cell cycle-dependent kinase CDK family is an indispensable protein family in the cell cycle,and the corresponding cyclin cyclin interacts with each other to regulate the normal progression of the cell cycle.CDK1 is the most important thing.It interacts with cyclinA and B to regulate the transformation of cells from G2 to M,thus ensuring the correct entry and exit of mitosis.Post-translational modification of proteins is a prerequisite for proteins to exert their normal physiological functions.Protein post-translational modification is one of the most popular topics in life sciences today.At present,more than 400post-translational modifications have been found,but only a dozen of them have been thoroughly studied.Crotonylation is a novel acylation modification found on histones in 2011.Its mechanism of action is similar to that of acyltransferase and deacyltransferase used in acetylation,and can also occur on histone lysine residues.However,its physiological role is different from acetylation,which promotes the interaction between histones and transcriptional promoter regions and enhancers,increases the transcription level of target genes,and plays a key role in the late stage of meiosis,which is related to spermatogenesis.Although crotonylation mainly occurs on histones,it has also been reported that crotonylation is also observed on non-histones,and there are data demonstrating that crotonylation can block the G2/M phase of the cell cycle.So we speculate whether crotonylation will occur on CDK1,which plays an important role in the cell cycle.What is the molecular mechanism?In this paper,the temporal and spatial dynamics of the crotonylation modificationof the key protein CDK1 and its regulation were investigated and verified.By analyzing the three-dimensional structure of CDK1 protein,we believe that CDK1-K139 is adjacent to the ATP-binding pocket and is also close to the activation loop.Therefore,the crotonylation modification at this site is likely to regulate CDK1 activity,and CDK1-K139 mutation is found in the yeast system.Compared with the wild type,its activity and function are affected,which hinders the growth of yeast and produces G2/M phase arrest.It has been reported that deacetylase HDACs,Sirts and acetyltransferase HATs,which play a regulatory role in acetylation,also regulate crotonylation,so we also explore which enzymes and CDK1 in these enzymes are more Good affinity.The study of these mechanisms has helped to deepen our understanding of the non-histone crotonylation modification and laid the foundation for a deep understanding of the cell cycle.