Arginine methylation regulates the p53 response

• DOI: 10.1038/ncb1802
• Publication Date: 2008-11-16T18:27:56Z
• Authors: Martin Jansson; Stephen T. Durant; Er-Chieh Cho; Sharon Sheahan; Mariola Edelmann; Benedikt Kessler; Nicholas B. La Th...
• Keywords: 0301 basic medicine; Protein-Arginine N-Methyltransferases; Molecular Sequence Data; Apoptosis; Arginine; Methylation; Protein Transport; 03 medical and health sciences; Humans; Mutant Proteins; Amino Acid Sequence; Protein Methyltransferases; Tumor Suppressor Protein p53; Carrier Proteins; Protein Structure, Quaternary; HeLa Cells; Protein Binding

Activation of the p53 tumour suppressor protein in response to DNA damage leads to apoptosis or cell-cycle arrest. Enzymatic modifications are widely believed to affect and regulate p53 activity. We describe here a level of post-translational control that has an important functional consequence on the p53 response. We show that the protein arginine methyltransferase (PRMT) 5, as a co-factor in a DNA damage responsive co-activator complex that interacts with p53, is responsible for methylating p53. Arginine methylation is regulated during the p53 response and affects the target gene specificity of p53. Furthermore, PRMT5 depletion triggers p53-dependent apoptosis. Thus, methylation on arginine residues is an underlying mechanism of control during the p53 response.