title: Diverse p63 and p73 isoforms regulate Δ133p53 expression through modulation of the internal TP53 promoter activity.
abstract: In response to stress, p53 binds and transactivates the internal TP53 promoter, thus regulating the expression of its own isoform, Δ133p53α. Here, we report that, in addition to p53, at least four p63/p73 isoforms regulate Δ133p53 expression at transcriptional level: p63β, ΔNp63α, ΔNp63β and ΔNp73γ. This regulation occurs through direct DNA-binding to the internal TP53 promoter as demonstrated by chromatin immunoprecipitation and the use of DNA-binding mutant p63. The promoter regions involved in the p63/p73-mediated transactivation were identified using deleted, mutant and polymorphic luciferase reporter constructs. In addition, we observed that transient expression of p53 family members modulates endogenous Δ133p53α expression at both mRNA and protein levels. We also report concomitant variation of p63 and Δ133p53 expression during keratinocyte differentiation of HaCat cells and induced pluripotent stem cells derived from mutated p63 ectodermal dysplasia patients. Finally, proliferation assays indicated that Δ133p53α isoform regulates the anti-proliferative activities of p63β, ΔNp63α, ΔNp63β and ΔNp73γ. Overall, this study shows a strong interplay between p53, p63 and p73 isoforms to orchestrate cell fate outcome.
authors.affiliation: Centre for Oncology and Molecular Medicine, INSERM-European Associated Laboratory, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland, UK.
authors.forename: V
authors.initials: V
authors.lastname: Marcel
authors.forename: I
authors.initials: I
authors.lastname: Petit
authors.forename: F
authors.initials: F
authors.lastname: Murray-Zmijewski
authors.forename: T
authors.initials: T
authors.lastname: Goullet de Rugy
authors.forename: K
authors.initials: K
authors.lastname: Fernandes
authors.forename: V
authors.initials: V
authors.lastname: Meuray
authors.forename: A
authors.initials: A
authors.lastname: Diot
authors.forename: D P
authors.initials: DP
authors.lastname: Lane
authors.forename: D
authors.initials: D
authors.lastname: Aberdam
authors.forename: J-C
authors.initials: JC
authors.lastname: Bourdon
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C115051:TP63 protein, human; C000606460:TP73 protein, human; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins
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