title: Arginine methylation regulates the p53 response.
abstract: 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.
authors.affiliation: Laboratory of Cancer Biology, Department of Clinical Pharmacology, Medical Sciences Division, University of Oxford, Old Road Campus Research Building, Old Road Campus, off Roosevelt Drive, Oxford, OX3 7DQ, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Jansson
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Durant
authors.forename: Er-Chieh
authors.initials: EC
authors.lastname: Cho
authors.forename: Sharon
authors.initials: S
authors.lastname: Sheahan
authors.forename: Mariola
authors.initials: M
authors.lastname: Edelmann
authors.forename: Benedikt
authors.initials: B
authors.lastname: Kessler
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: La Thangue
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D001120:Arginine / Q000378:metabolism*; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D011485:Protein Binding; D011496:Protein Methyltransferases / Q000737:chemistry / Q000378:metabolism; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D011484:Protein-Arginine N-Methyltransferases; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D050505:Mutant Proteins; C434146:Strap protein; D016159:Tumor Suppressor Protein p53; D001120:Arginine; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases