Arginine Methylation Modification And Function Of P16 Protein

Many factors and genes have been correlated with the occurrence and development of cancers. Inactivation of the tumor suppressor genes or activation of the tumor genes is a basic molecular event during carcinogenesis. Therefore, reactivation of tumor suppressor genes may represent an option of gene therapy for cancers. p16 has been known as a tumor suppressor gene, which suppresses proliferation of cells via direct inhibition of cell cycle progression. The p16 protein binds specifically to CDK4 and CDK6 to prevent them from interacting with cyclin D, and prevents G1/S cell cycle progression and cell proliferation. Accordingly, p16 is a potential target for cancer gene therapy. Previous studies have demonstrated that the phosphorylation of Ser152 of p16 protein promotes the interaction of p16 and CDK4, suggesting that the post-translational modification of p16 participate in the regulation of p16 function. Whether other modification of p16 protein participates in its function has not been elucidated. In our study, we found that the arginine of p16 was methylated. Arg22 , Arg131 and Arg138 play the key roles in the arginine methylationo of p16 protein, and the p16 with the mutations of these sites arrests the cell cycle at G1 phase, effectively, suggesting the arginine methylation affect the function of p16 protein.In this study, we preliminary explore the post-translational modification affects p16 function and provide the new experimental basis for funther anderstanding the molecular mechanism of p16 function.