Molecular basis for modulation of the p53 target selectivity by KLF4.
The tumour suppressor p53 controls transcription of various genes involved in apoptosis, cell-cycle arrest, DNA repair and metabolism. However, its DNA-recognition specificity is not nearly sufficient to explain binding to specific locations in vivo. Here, we present evidence that KLF4 increases the...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3484126?pdf=render |
| _version_ | 1818555709762043904 |
|---|---|
| author | Tobias Brandt Fiona M Townsley Daniel P Teufel Stefan M V Freund Dmitry B Veprintsev |
| author_facet | Tobias Brandt Fiona M Townsley Daniel P Teufel Stefan M V Freund Dmitry B Veprintsev |
| author_sort | Tobias Brandt |
| collection | DOAJ |
| description | The tumour suppressor p53 controls transcription of various genes involved in apoptosis, cell-cycle arrest, DNA repair and metabolism. However, its DNA-recognition specificity is not nearly sufficient to explain binding to specific locations in vivo. Here, we present evidence that KLF4 increases the DNA-binding affinity of p53 through the formation of a loosely arranged ternary complex on DNA. This effect depends on the distance between the response elements of KLF4 and p53. Using nuclear magnetic resonance and fluorescence techniques, we found that the amino-terminal domain of p53 interacts with the KLF4 zinc fingers and mapped the interaction site. The strength of this interaction was increased by phosphorylation of the p53 N-terminus, particularly on residues associated with regulation of cell-cycle arrest genes. Taken together, the cooperative binding of KLF4 and p53 to DNA exemplifies a regulatory mechanism that contributes to p53 target selectivity. |
| first_indexed | 2024-12-12T09:57:09Z |
| format | Article |
| id | doaj.art-d850e05a4903400c91ade8c35fc6b816 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T09:57:09Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d850e05a4903400c91ade8c35fc6b8162022-12-22T00:28:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4825210.1371/journal.pone.0048252Molecular basis for modulation of the p53 target selectivity by KLF4.Tobias BrandtFiona M TownsleyDaniel P TeufelStefan M V FreundDmitry B VeprintsevThe tumour suppressor p53 controls transcription of various genes involved in apoptosis, cell-cycle arrest, DNA repair and metabolism. However, its DNA-recognition specificity is not nearly sufficient to explain binding to specific locations in vivo. Here, we present evidence that KLF4 increases the DNA-binding affinity of p53 through the formation of a loosely arranged ternary complex on DNA. This effect depends on the distance between the response elements of KLF4 and p53. Using nuclear magnetic resonance and fluorescence techniques, we found that the amino-terminal domain of p53 interacts with the KLF4 zinc fingers and mapped the interaction site. The strength of this interaction was increased by phosphorylation of the p53 N-terminus, particularly on residues associated with regulation of cell-cycle arrest genes. Taken together, the cooperative binding of KLF4 and p53 to DNA exemplifies a regulatory mechanism that contributes to p53 target selectivity.http://europepmc.org/articles/PMC3484126?pdf=render |
| spellingShingle | Tobias Brandt Fiona M Townsley Daniel P Teufel Stefan M V Freund Dmitry B Veprintsev Molecular basis for modulation of the p53 target selectivity by KLF4. PLoS ONE |
| title | Molecular basis for modulation of the p53 target selectivity by KLF4. |
| title_full | Molecular basis for modulation of the p53 target selectivity by KLF4. |
| title_fullStr | Molecular basis for modulation of the p53 target selectivity by KLF4. |
| title_full_unstemmed | Molecular basis for modulation of the p53 target selectivity by KLF4. |
| title_short | Molecular basis for modulation of the p53 target selectivity by KLF4. |
| title_sort | molecular basis for modulation of the p53 target selectivity by klf4 |
| url | http://europepmc.org/articles/PMC3484126?pdf=render |
| work_keys_str_mv | AT tobiasbrandt molecularbasisformodulationofthep53targetselectivitybyklf4 AT fionamtownsley molecularbasisformodulationofthep53targetselectivitybyklf4 AT danielpteufel molecularbasisformodulationofthep53targetselectivitybyklf4 AT stefanmvfreund molecularbasisformodulationofthep53targetselectivitybyklf4 AT dmitrybveprintsev molecularbasisformodulationofthep53targetselectivitybyklf4 |