Comparative binding of p53 to its promoter and DNA recognition elements.
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.
Weinberg
Richard L
RL
Cambridge University Chemical Laboratory and MRC Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, UK.
Veprintsev
Dmitry B
DB
Bycroft
Mark
M
Fersht
Alan R
AR
D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics; D005786:Gene Expression Regulation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020218:Response Elements; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D016159:Tumor Suppressor Protein p53