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Regulation of p53 activity through lysine methylation
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 S...
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| Published in: | Nature 2004-11, Vol.432 (7015), p.353-360 |
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| Main Authors: | , , , , , , , , , , , |
| Format: | Article |
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| cites | cdi_FETCH-LOGICAL-c647t-f7dfccd1542bd0c3da9740fb8313968e7b957b778b41428a746ae4ac08eb17e23 |
| container_end_page | 360 |
| container_issue | 7015 |
| container_start_page | 353 |
| container_title | Nature |
| container_volume | 432 |
| creator | Barlev, Nickolai A Reinberg, Danny Chuikov, Sergei Kurash, Julia K Wilson, Jonathan R Xiao, Bing Justin, Neil Ivanov, Gleb S McKinney, Kristine Tempst, Paul Prives, Carol Gamblin, Steven J |
| description | 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. |
| doi_str_mv | 10.1038/nature03117 |
| format | article |
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S
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S
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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
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| fulltext | fulltext |
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| ispartof | Nature, 2004-11, Vol.432 (7015), p.353-360 |
| issn | 0028-0836 1476-4687 |
| language | eng |
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| source | Nature |
| subjects | Amino Acid Sequence Apoptosis Cell Line Cell Nucleus - metabolism Gene expression Gene Expression Regulation Genes, p53 - genetics Genes, ras - genetics Histone-Lysine N-Methyltransferase - chemistry Histone-Lysine N-Methyltransferase - genetics Histone-Lysine N-Methyltransferase - metabolism Humanities and Social Sciences Humans Lysine - metabolism Methylation Models, Molecular Molecular Sequence Data multidisciplinary Promoter Regions, Genetic - genetics Protein Binding Protein Conformation Protein Methyltransferases Proteins RNA, Messenger - genetics RNA, Messenger - metabolism S-Adenosylhomocysteine - metabolism Science Science (multidisciplinary) Substrate Specificity Thermodynamics Tumor Suppressor Protein p53 - chemistry Tumor Suppressor Protein p53 - metabolism Tumors |
| title | Regulation of p53 activity through lysine methylation |
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