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Arginine methylation of hnRNPK negatively modulates apoptosis upon DNA damage through local regulation of phosphorylation.

Yang JH, Chiou YY, Fu SL, Shih IY, Weng TH, Lin WJ, Lin CH - Nucleic Acids Res. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang Ming University, Taipei 11221, Taiwan.

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Supplementing with exogenous hnRNPK carrying R296/R299 methylation reduced U2OS-K-2RK cell apoptosis after DNA damage. The U2OS-K-2RK cells were transfected with shRNA-resistant WT or 3RK-2 mutant (R256K/ R258K/ R268K) hnRNPKs, followed by etoposide treatment for 12 h. The expression levels of hnRNPK, GAPDH and cleaved caspase 3 were determined using specific antibodies.
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Figure 8: Supplementing with exogenous hnRNPK carrying R296/R299 methylation reduced U2OS-K-2RK cell apoptosis after DNA damage. The U2OS-K-2RK cells were transfected with shRNA-resistant WT or 3RK-2 mutant (R256K/ R258K/ R268K) hnRNPKs, followed by etoposide treatment for 12 h. The expression levels of hnRNPK, GAPDH and cleaved caspase 3 were determined using specific antibodies.

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 PKCĪ“-mediated apoptosis upon DNA damage.


Arginine methylation of hnRNPK negatively modulates apoptosis upon DNA damage through local regulation of phosphorylation.

Yang JH, Chiou YY, Fu SL, Shih IY, Weng TH, Lin WJ, Lin CH - Nucleic Acids Res. (2014)

Supplementing with exogenous hnRNPK carrying R296/R299 methylation reduced U2OS-K-2RK cell apoptosis after DNA damage. The U2OS-K-2RK cells were transfected with shRNA-resistant WT or 3RK-2 mutant (R256K/ R258K/ R268K) hnRNPKs, followed by etoposide treatment for 12 h. The expression levels of hnRNPK, GAPDH and cleaved caspase 3 were determined using specific antibodies.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150800&req=5

Figure 8: Supplementing with exogenous hnRNPK carrying R296/R299 methylation reduced U2OS-K-2RK cell apoptosis after DNA damage. The U2OS-K-2RK cells were transfected with shRNA-resistant WT or 3RK-2 mutant (R256K/ R258K/ R268K) hnRNPKs, followed by etoposide treatment for 12 h. The expression levels of hnRNPK, GAPDH and cleaved caspase 3 were determined using specific antibodies.
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 PKCĪ“-mediated apoptosis upon DNA damage.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang Ming University, Taipei 11221, Taiwan.

Show MeSH
Related in: MedlinePlus