Affordable Access

deepdyve-link
Publisher Website

P63 modulates the expression of the WDFY2 gene which is implicated in cancer regulation and limb development.

Authors
  • Monti, Paola1
  • Ciribilli, Yari2
  • Foggetti, Giorgia1
  • Menichini, Paola1
  • Bisio, Alessandra2
  • Cappato, Serena3
  • Inga, Alberto2
  • Divizia, Maria Teresa4
  • Lerone, Margherita4
  • Bocciardi, Renata3, 4
  • Fronza, Gilberto1
  • 1 Mutagenesis and Cancer Prevention Unit, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi, 10, Genoa 16132, Italy. , (Italy)
  • 2 Department of Cellular, Computational and Integrative Biology (CIBio), University of Trento, Via Sommarive 9, Povo (TN) 38123, Italy. , (Italy)
  • 3 Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Largo P. Daneo, 3, Genoa 16132, Italy. , (Italy)
  • 4 Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Via G. Gaslini, 5, Genoa 16147, Italy. , (Italy)
Type
Published Article
Journal
Bioscience Reports
Publisher
Portland Press
Publication Date
Dec 20, 2019
Volume
39
Issue
12
Identifiers
DOI: 10.1042/BSR20192114
PMID: 31789342
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

TP63 is a member of the TP53 gene family, sharing a common gene structure that produces two groups of mRNAs' encoding proteins with different N-terminal regions (ΔN and TA isoforms); both transcripts are also subjected to alternative splicing mechanisms at C-terminus, generating a variety of isoforms. p63 is a master regulator of epidermal development and homoeostasis as well as an important player in tumorigenesis and cancer progression with both oncogenic and tumour suppressive roles. A number of studies have aimed at the identification of p63 target genes, allowing the dissection of the molecular pathways orchestrated by the different isoforms. In the present study we investigated in more detail the p63 responsiveness of the WDFY2 (WD repeat and FYVE domain containing 2) gene, encoding for an endosomal protein identified as a binding partner of the PI-3K/AKT signalling pathway. We showed that overexpression of different p63 isoforms was able to induce WDFY2 expression in TP53-null cells. The p63-dependent transcriptional activation was associated with specific response elements (REs) that have been identified by a bioinformatics tool and validated by yeast- and mammal-based assays. Interestingly, to confirm that WDFY2 belongs to the p63 network of cancer regulation, we analysed the impact of WDFY2 alterations, by showing its frequent deletion in different types of tumours and suggesting its expression level as a prognostic biomarker. Lastly, we identified a chromosomal translocation involving the WDFY2 locus in a patient affected by a rare congenital limb anomaly, indicating WDFY2 as a possible susceptibility gene placed downstream p63 in the network of limb development. © 2019 The Author(s).

Report this publication

Statistics

Seen <100 times