Nucleic Acids Research Advance Access originally published online on August 21, 2009
Nucleic Acids Research 2009 37(18):6092-6104; doi:10.1093/nar/gkp674
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Nucleic Acids Research, 2009, Vol. 37, No. 18 6092-6104
© The Author 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses?by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Genomics |
Identification and functional characterization of two new transcriptional variants of the human p63 gene
1Dipartimento di Biochimica e Biologia Molecolare "E. Quagliariello", Università degli Studi di Bari, via Orabona 4, 70126 Bari and 2Istituto di Tecnologie Biomediche, Consiglio Nazionale delle Ricerche, via Amendola 122/D, 70125 Bari, Italy
*To whom correspondence should be addressed. Tel: +39 080 5443588; Fax: +39 080 5443317; Email: graziano.pesole{at}biologia.uniba.it
Correspondence may also be addressed to Anna Maria D’Erchia. Tel: +39 080 5443304; Fax: +39 080 5443317; Email: annamaria.derchia{at}biologia.uniba.it
Received May 31, 2009. Revised July 2, 2009. Accepted July 30, 2009.
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 
N) which are alternatively spliced at the C-terminus. Here, we report the identification of two new C-terminus p63 variants, we named p63 
and 
, 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 N 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 Np63
, Np63 and 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.