1. Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
2. Molecular Oncology Research Institute, NEMC-Tufts School of Medicine, 75 Kneeland Street, Boston, Massachusetts 02111, USA
3. Structural Biology Group, MRC-NIMR, The Ridgeway, Mill Hill, London NW7 1AA, UK
4. Department of Biological Sciences, Columbia University, New York, New York 10027, USA
5. Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA

Correspondence to: Nickolai A. Barlev²Danny Reinberg¹ Email: reinbedf@UMDNJ.EDU
Email: nbarlev@tufts-nemc.org
Coordinates have been deposited in the Protein Data Bank under accession code 1XQH.

Abstract

p53 is a tumour suppressor that regulates the cellular response to genotoxic stresses. p53 is a short-lived protein and its activity is regulated mostly by stabilization via different post-translational modifications. Here we report a novel mechanism of p53 regulation through lysine methylation by Set9 methyltransferase. Set9 specifically methylates p53 at one residue within the carboxyl-terminus regulatory region. Methylated p53 is restricted to the nucleus and the modification positively affects its stability. Set9 regulates the expression of p53 target genes in a manner dependent on the p53-methylation site. The crystal structure of a ternary complex of Set9 with a p53 peptide and the cofactor product S-adenosyl-l-homocysteine (AdoHcy) provides the molecular basis for recognition of p53 by this lysine methyltransferase.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.