Human Gene Set: INGA_TP53_TARGETS

Standard name INGA_TP53_TARGETS
Systematic name M16284
Brief description Genes whose promoters contain TP53 [GeneID=7157] response elements.
Full description or abstract Little is known about the mechanisms that regulate differential transactivation by p53. We developed a system in the yeast Saccharomyces cerevisiae that addresses p53 transactivation capacity from 26 different p53 response elements (REs) under conditions where all other factors, such as chromatin, are kept constant. The system relies on a tightly regulated promoter (rheostatable) that can provide for a broad range of p53 expression. The p53 transactivation capacity toward each 20- to 22-bp-long RE could be ranked by using a simple phenotypic assay. Surprisingly, there was as much as a 1,000-fold difference in transactivation. There was no correlation between the functional rank and statistical predictions of binding energy of the REs. Instead we found that the central sequence element in an RE greatly affects p53 transactivation capacity, possibly because of DNA structural properties. Our results suggest that intrinsic DNA binding affinity and p53 protein levels are important contributors to p53-induced differential transactivation. These results are also relevant to understanding the regulation by other families of transcription factors that recognize several sequence-related response elements and/or have tightly regulated expression. We found that p53 had weak activity towards half the apoptotic REs. In addition, p53 alleles associated with familial breast cancer, previously classified as wild type, showed subtle differences in transactivation capacity towards several REs.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12446780   Authors: Inga A,Storici F,Darden TA,Resnick MA
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Source species Homo sapiens
Contributed by John Newman (University of Washington)
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Version history 3.0: Renamed from P53GENES_ALL

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