Regulation of p53 activity through lysine methylation Journal Article
| Authors: | Chuikov, S.; Kurash, J. K.; Wilson, J. R.; Xiao, B.; Justin, N.; Ivanov, G. S.; McKinney, K.; Tempst, P.; Prives, C.; Gamblin, S. J.; Barlev, N. A.; Reinberg, D. |
| Article Title: | Regulation of p53 activity through lysine methylation |
| 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. |
| Keywords: | methylation; nonhuman; protein conformation; proteins; animal cell; gene targeting; complex formation; reverse transcription polymerase chain reaction; apoptosis; carboxy terminal sequence; cell line; protein binding; protein stability; phosphorylation; protein p53; animalia; gene expression regulation; tumor suppressor gene; methyltransferase; amino acid sequence; molecular sequence data; tumors; rna, messenger; s-adenosylhomocysteine; histone-lysine n-methyltransferase; substrate specificity; tumor suppressor protein p53; crystal structure; models, molecular; thermodynamics; cell nucleus; genes, ras; protein tertiary structure; lysine; derivatization; protein modification; acetylation; genes, p53; genotoxicity; protein synthesis regulation; s adenosylhomocysteine; promoter regions (genetics); cellular response; cancer; humans; priority journal; article; tumour suppressors |
| Journal Title: | Nature |
| Volume: | 432 |
| Issue: | 7015 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2004-11-18 |
| Start Page: | 353 |
| End Page: | 360 |
| Language: | English |
| DOI: | 10.1038/nature03117 |
| PROVIDER: | scopus |
| PUBMED: | 15525938 |
| DOI/URL: | |
| Notes: | Nature -- Cited By (since 1996):357 -- Export Date: 16 June 2014 -- CODEN: NATUA -- Source: Scopus |
