title: Identification and functional characterization of two new transcriptional variants of the human p63 gene.
abstract: p63 belongs to a family of transcription factors, which, while demonstrating striking conservation of functional domains, regulate distinct biological functions. Its principal role is in the regulation of epithelial commitment, differentiation and maintenance programs, during embryogenesis and in adult tissues. The p63 gene has a complex transcriptional pattern, producing two subclasses of N-terminal isoforms (TA and DeltaN) which are alternatively spliced at the C-terminus. Here, we report the identification of two new C-terminus p63 variants, we named p63 delta and epsilon, that increase from 6 to 10 the number of the p63 isoforms. Expression analysis of all p63 variants demonstrates a tissue/cell-type-specific nature of p63 alternative transcript expression, probably related to their different cellular functions. We demonstrate that the new p63 variants as DeltaN isoforms are active as transcription factors as they have nuclear localization and can modulate the expression of p63 target genes. Moreover, we report that, like DeltaNp63alpha, DeltaNp63delta and epsilon sustain cellular proliferation and that their expression decreases during keratinocyte differentiation, suggesting their involvement in this process. Taken together, our results demonstrate the existence of novel p63 proteins whose expression should be considered in future studies on the roles of p63 in the regulation of cellular functions.
authors.affiliation: Dipartimento di Biochimica e Biologia Molecolare E. Quagliariello, Università degli Studi di Bari, via Orabona 4, 70126 Bari, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Mangiulli
authors.forename: Alessio
authors.initials: A
authors.lastname: Valletti
authors.forename: Mariano Francesco
authors.initials: MF
authors.lastname: Caratozzolo
authors.forename: Apollonia
authors.initials: A
authors.lastname: Tullo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Sbisà
authors.forename: Graziano
authors.initials: G
authors.lastname: Pesole
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Erchia
mesh_terms: D000465:Algorithms; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000032:analysis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D020033:Protein Isoforms; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
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