Arginine methylation of hnRNPK negatively modulates apoptosis upon DNA damage through local regulation of phosphorylation.
Bottom Line: In addition, increased hnRNPK expression has been associated with tumor development and progression.In the present study, we demonstrated that the methylation of two essential arginines, Arg296 and Arg299, on hnRNPK inhibited a nearby Ser302 phosphorylation that was mediated through the pro-apoptotic kinase PKCδ.While such elevated apoptosis can be diminished through addition with wild-type hnRNPK, we further demonstrated that this increased apoptosis occurred through both intrinsic and extrinsic pathways and was p53 independent, at least in part.
Affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang Ming University, Taipei 11221, Taiwan.Show MeSH
Related in: MedlinePlus
Mentions: To further validate the negative role of hnRNPK methylation on apoptosis induction, we expressed either the shRNA-resistant WT hnRNPK or shRNA-resistant 3RK-2 (R256K/R258K/R268K) hnRNPK mutants in the etoposide-treated U2OS-K-2RK cells. As shown in Figure 8, supplementing these cells with Arg296/Arg299-methylable hnRNPKs resulted in reduced caspase 3 cleavage compared with the vector control. This result indicates that methylation at arginine residues 296 and 299 of hnRNPK indeed suppresses PKCδ-mediated apoptosis upon DNA damage.
Affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang Ming University, Taipei 11221, Taiwan.