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 
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.
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Metadaten
Author:Tobias Brandt, Fiona M. Townsley, Daniel P. Teufel, Stefan M. V. Freund, Dmitry B. Veprintsev
URN:urn:nbn:de:hebis:30:3-265849
DOI:http://dx.doi.org/10.1371/journal.pone.0048252
ISSN:1932-6203
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=23118962
Parent Title (English):Plos one
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2012/10/30
Date of first Publication:2012/10/30
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2012/11/05
Volume:7
Issue:(10): e48252
Pagenumber:11
First Page:1
Last Page:11
Note:
Copyright: © 2012 Brandt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Institutes:Biowissenschaften
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sondersammelgebiets-Volltexte
Licence (German):License LogoArchivex. zur Lesesaalplatznutzung § 52b UrhG

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