The interplay between p16 serine phosphorylation and arginine methylation determines its function in modulating cellular apoptosis and senescence.
The interplay between p16 serine phosphorylation and arginine methylation determines its function in modulating cellular apoptosis and senescence.
复制标题
p16 丝氨酸磷酸化和精氨酸甲基化之间的相互作用决定了其调节细胞凋亡和衰老的功能
DOI：
10.1038/srep41390
复制
发表时间：
2017-01-25
影响因子：
4.6
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Lu Y;Ma W;Li Z;Lu J;Wang X
Cyclin-dependent kinase inhibitor p16INK4a(p16) primarily functions as a negative regulator of the retinoblastoma protein (Rb) -E2F pathway, thus plays critical role in cell cycle progression, cellular senescence and apoptosis. In this study, we showed that the methylation of Arg 138 and the phosphorylation of Ser 140 on p16 were critical for the control of cell proliferation and apoptosis. Compared to wild type p16, mutant p16R138K possessed improved function in preventing cell proliferation and inducing apoptosis, while the Ser 140 mutation (p16S140A) exhibited the opposite alteration. We also demonstrated that H2O2was able to induce the phosphorylation of p16, which facilitated the interaction between CDK4 (Cyclin-dependent protein kinase) and p16, in 293T (human emborynic kidney) cells. Furthermore, the elevated arginine methylation in p16S140A mutant and increased serine phosphorylation in p16R138K mutant suggest that a antagonizing mechanism coordinating Arg 138 methylation and Ser 140 phosphorylation to regulates p16 function as well as cellular apoptosis and senescence. These findings will therefore contribute to therapeutic treatment for p16-related gene therapy by providing theoretical and experimental evidence.
