title: p53 basic C terminus regulates p53 functions through DNA binding modulation of subset of target genes.
abstract: The p53 gene encodes a transcription factor that is composed of several functional domains: the N-terminal transactivation domain, the central sequence-specific DNA binding domain, the tetramerization domain, and the highly basic C-terminal regulatory domain (CTD). The p53 CTD is a nonspecific DNA binding domain that is subject to extensive post-translational modifications. However, the functional significance of the p53 CTD remains unclear. The role of this domain in the regulation of p53 functions is explored by comparing the activity of ectopically expressed wild-type (WT) p53 protein to that of a truncated mutant lacking the 24 terminal amino acids (Δ24). Using quantitative real time PCR and chromatin Immuno-Precipitation experiments, a p53 CTD deletion is shown to alter the p53-dependent induction of a subset of its target genes due to impaired specific DNA binding. Moreover, p53-induced growth arrest and apoptosis both require an intact p53 CTD. These data indicate that the p53 CTD is a positive regulator of p53 tumor suppressor functions.
authors.affiliation: Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Pierre-Jacques
authors.initials: PJ
authors.lastname: Hamard
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Lukin
authors.forename: James J
authors.initials: JJ
authors.lastname: Manfredi
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D019070:Cell Lineage; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000596:Amino Acids; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004247:DNA; D001973:Bromodeoxyuridine