title: ∆N-P63α and TA-P63α exhibit intrinsic differences in transactivation specificities that depend on distinct features of DNA target sites.
abstract: TP63 is a member of the TP53 gene family that encodes for up to ten different TA and ∆N isoforms through alternative promoter usage and alternative splicing. Besides being a master regulator of gene expression for squamous epithelial proliferation, differentiation and maintenance, P63, through differential expression of its isoforms, plays important roles in tumorigenesis. All P63 isoforms share an immunoglobulin-like folded DNA binding domain responsible for binding to sequence-specific response elements (REs), whose overall consensus sequence is similar to that of the canonical p53 RE. Using a defined assay in yeast, where P63 isoforms and RE sequences are the only variables, and gene expression assays in human cell lines, we demonstrated that human TA- and ∆N-P63α proteins exhibited differences in transactivation specificity not observed with the corresponding P73 or P53 protein isoforms. These differences 1) were dependent on specific features of the RE sequence, 2) could be related to intrinsic differences in their oligomeric state and cooperative DNA binding, and 3) appeared to be conserved in evolution. Sicen genotoxic stress can change relative ratio of TA- and ∆N-P63α protein levels, the different transactivation specificity of each P63 isoform could potentially influence cellular responses to specific stresses.
authors.forename: Paola
authors.initials: P
authors.lastname: Monti
authors.forename: Yari
authors.initials: Y
authors.lastname: Ciribilli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bisio
authors.forename: Giorgia
authors.initials: G
authors.lastname: Foggetti
authors.forename: Ivan
authors.initials: I
authors.lastname: Raimondi
authors.forename: Paola
authors.initials: P
authors.lastname: Campomenosi
authors.forename: Paola
authors.initials: P
authors.lastname: Menichini
authors.forename: Gilberto
authors.initials: G
authors.lastname: Fronza
authors.forename: Alberto
authors.initials: A
authors.lastname: Inga
mesh_terms: D015153:Blotting, Western; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000378:metabolism; D020218:Response Elements / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D020033:Protein Isoforms; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D004247:DNA