Arginine methylation regulates the p53 response

The tumour suppressor p53 is subject to complex regulation and arginine methylation is now shown to provide an additional level of control. The protein arginine methyltransferase (PRMT) 5 is recruited by Strap to methylate p53 in response to DNA damage, governing the p53 response. Activation of the...

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Veröffentlicht in:Nature cell biology Jg. 10; H. 12; S. 1431 - 1439
Hauptverfasser: Jansson, Martin, Durant, Stephen T., Cho, Er-Chieh, Sheahan, Sharon, Edelmann, Mariola, Kessler, Benedikt, La Thangue, Nicholas B.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 01.12.2008
Nature Publishing Group
Schlagworte:
Amino Acid Sequence
Apoptosis
Arginine - metabolism
Biomedical and Life Sciences
Cancer Research
Carrier Proteins - isolation & purification
Carrier Proteins - metabolism
Cell Biology
Cyclin-dependent kinases
Deoxyribonucleic acid
Developmental Biology
DNA
DNA damage
DNA methylation
HeLa Cells
Humans
Kinases
Life Sciences
Methylation
Molecular Sequence Data
Mutant Proteins - metabolism
Phosphorylation
Polypeptides
Protein Binding
Protein Methyltransferases - chemistry
Protein Methyltransferases - metabolism
Protein Structure, Quaternary
Protein Transport
Protein-Arginine N-Methyltransferases
Proteins
Stem Cells
Tumor Suppressor Protein p53 - metabolism
United Kingdom > UK
ISSN:1465-7392, 1476-4679, 1476-4679
Online-Zugang:Volltext
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Zusammenfassung:The tumour suppressor p53 is subject to complex regulation and arginine methylation is now shown to provide an additional level of control. The protein arginine methyltransferase (PRMT) 5 is recruited by Strap to methylate p53 in response to DNA damage, governing the p53 response. 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.
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ISSN:1465-7392
1476-4679
1476-4679
DOI:10.1038/ncb1802