title: Effect of phosphorylation and methylation on the function of the p16INK4aprotein in non-small cell lung cancer A549 cells.
abstract: The p16INK4aprotein (p16) has been reported to be a tumor suppressor gene that suppresses the proliferation of cells through the direct inhibition of cell cycle progression. Accordingly, p16 is a potential target for cancer gene therapy. In the present study, the arginine 22, 131 and 138 residues of p16 were found to be methylation sites, as the mutation of these arginine residues to lysine resulted in the hypomethylation of p16. Furthermore, the protein arginine methyltransferases (PRMTs), such as PRMT1, PRMT4 and PRMT6, were determined to be involved in the methylation of the p16 arginine residues. PRMT6 effectively reduced the intensity of the association between p16 and CDK4, and also weakened the function of p16 in preventing cell proliferation. In addition, the p16 protein was found to be phosphorylated in various cell lines, and mutations in the serine residues weakened the cell cycle arrest and induction of apoptosis mediated by p16. Preliminarily, the crosstalk between the phosphorylation and arginine methylation modification of p16 was examined. These findings predict a role for serine phosphorylation against arginine methylation of p16.
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, P.R. China.
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Ma
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, P.R. China.
authors.forename: Ling-Xia
authors.initials: LX
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, P.R. China.
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Wang
keywords: arginine; methylation; p16; phosphorylation; protein arginine methyltransferase; serine