Role of p53 Serine 46 in p53 Target Gene Regulation
| Autor: | Simon J. van Heeringen, Eva M. Janssen-Megens, Bianca Gilbert, Max Koeppel, Hendrik G. Stunnenberg, Leonie Smeenk, Marion Lohrum |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
lcsh:Medicine
Serine Transcriptome chemistry.chemical_compound Phosphoserine Sequence Analysis Protein Gene expression Molecular Cell Biology Cluster Analysis Phosphorylation lcsh:Science GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) Cellular Stress Responses Etoposide Regulation of gene expression Multidisciplinary Cell Death Genomics Chromatin Cell biology Functional Genomics Gene Expression Regulation Neoplastic Dactinomycin Research Article Protein Binding Chromatin Immunoprecipitation DNA transcription Cell fate determination Biology Cell Growth Molecular Genetics Structure-Activity Relationship ddc:570 Cell Line Tumor Genetics Cancer Genetics Humans Gene Regulation Molecular Biology Binding Sites Genome Human lcsh:R Molecular Sequence Annotation DNA Molecular biology chemistry lcsh:Q Gene Function Tumor Suppressor Protein p53 Genome Expression Analysis |
| Zdroj: | PLoS ONE PLoS One, 6, 3 PLoS ONE, Vol 6, Iss 3, p e17574 (2011) PLoS One, 6 |
| ISSN: | 1932-6203 |
| Popis: | The tumor suppressor p53 plays a crucial role in cellular growth control inducing a plethora of different response pathways. The molecular mechanisms that discriminate between the distinct p53-responses have remained largely elusive. Here, we have analyzed the p53-regulated pathways induced by Actinomycin D and Etoposide treatment resulting in more growth arrested versus apoptotic cells respectively. We found that the genome-wide p53 DNA-binding patterns are almost identical upon both treatments notwithstanding transcriptional differences that we observed in global transcriptome analysis. To assess the role of post-translational modifications in target gene choice and activation we investigated the genome-wide level of phosphorylation of Serine 46 of p53 bound to DNA (p53-pS46) and of Serine 15 (p53-pS15). Interestingly, the extent of S46 phosphorylation of p53 bound to DNA is considerably higher in cells directed towards apoptosis while the degree of phosphorylation at S15 remains highly similar. Moreover, our data suggest that following different chemotherapeutical treatments, the amount of chromatin-associated p53 phosphorylated at S46 but not at pS15 is higher on certain apoptosis related target genes. Our data provide evidence that cell fate decisions are not made primarily on the level of general p53 DNA-binding and that post-translationally modified p53 can have distinct DNA-binding characteristics. |
| Databáze: | OpenAIRE |
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