Comparative binding of p53 to its promoter and DNA recognition elements
- PMID: 15826656
- DOI: 10.1016/j.jmb.2005.03.014
Comparative binding of p53 to its promoter and DNA recognition elements
Abstract
Tumor suppressor p53 is a transcription factor that transactivates a wide range of genes, including those in DNA repair, cell cycle arrest, apoptosis and its own degradation. To estimate the role of selectivity in binding to its promoters, we measured the binding affinities of a tetrameric p53 construct (p53CT) in vitro with 20 of its recognition elements from a variety of representative genes. The binding of full length p53 to four representative sequences exactly paralleled the affinities to p53CT. The binding of p53 to different recognition elements was co-operative and the affinities varied by up to 50-fold. p53 bound with high affinity to the recognition elements of all the genes involved in cell cycle arrest and some of the genes in apoptosis. All of the lower affinity-binding sites were in genes involved in apoptosis. Our quantitative-binding data were in agreement with published cell-based assays. The regulation of p53 activity is in part determined through the specificity of its DNA-binding interactions.
Similar articles
-
Physical and functional interactions between members of the tumour suppressor p53 and the Sp families of transcription factors: importance for the regulation of genes involved in cell-cycle arrest and apoptosis.Biochem J. 2005 Jul 15;389(Pt 2):443-55. doi: 10.1042/BJ20041980. Biochem J. 2005. PMID: 15790310 Free PMC article.
-
Multiple response elements and differential p53 binding control Perp expression during apoptosis.Mol Cancer Res. 2003 Dec;1(14):1048-57. Mol Cancer Res. 2003. PMID: 14707288
-
DNA binding cooperativity of p53 modulates the decision between cell-cycle arrest and apoptosis.Mol Cell. 2010 May 14;38(3):356-68. doi: 10.1016/j.molcel.2010.02.037. Mol Cell. 2010. PMID: 20471942
-
Transcriptional control of human p53-regulated genes.Nat Rev Mol Cell Biol. 2008 May;9(5):402-12. doi: 10.1038/nrm2395. Nat Rev Mol Cell Biol. 2008. PMID: 18431400 Review.
-
Transcriptional regulation by p53: one protein, many possibilities.Cell Death Differ. 2006 Jun;13(6):951-61. doi: 10.1038/sj.cdd.4401916. Cell Death Differ. 2006. PMID: 16575405 Review.
Cited by
-
A Hill type equation can predict target gene expression driven by p53 pulsing.FEBS Open Bio. 2021 Jun;11(6):1799-1808. doi: 10.1002/2211-5463.13179. Epub 2021 May 27. FEBS Open Bio. 2021. PMID: 33955710 Free PMC article.
-
Low-level p53 expression changes transactivation rules and reveals superactivating sequences.Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14387-92. doi: 10.1073/pnas.1205971109. Epub 2012 Aug 20. Proc Natl Acad Sci U S A. 2012. PMID: 22908277 Free PMC article.
-
Structural and functional implications of p53 missense cancer mutations.PMC Biophys. 2009 Jun 26;2(1):5. doi: 10.1186/1757-5036-2-5. PMC Biophys. 2009. PMID: 19558684 Free PMC article.
-
p53 pulses lead to distinct patterns of gene expression albeit similar DNA-binding dynamics.Nat Struct Mol Biol. 2017 Oct;24(10):840-847. doi: 10.1038/nsmb.3452. Epub 2017 Aug 21. Nat Struct Mol Biol. 2017. PMID: 28825732 Free PMC article.
-
Life and Death Decision-Making by p53 and Implications for Cancer Immunotherapy.Trends Cancer. 2021 Mar;7(3):226-239. doi: 10.1016/j.trecan.2020.10.005. Epub 2020 Nov 13. Trends Cancer. 2021. PMID: 33199193 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
