p63-Associated Disorders

Abstract

AcKnowledGemenTsWe thank Ben Hamel, Hans Scheffer and Rowdy Meijer in clinical and diagnostic investigations, and all p63 syndrome patients and clinicians all over the world, who have made this study feasible. Work in our laboratory is supported by European Union Sixth Framework programme EpiStem project (LSHB-CT-2005-019067). ABsTRAcTHeterozygous mutations in the transcription factor gene p63 are causative for several syndromes with ectodermal dysplasia, orofacial clefting and limb malformations as the key characteristics. Different combinations of these features are seen in five different syndromes, of which ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome (EEC) is the most common one. Mutations in p63 can also cause non-syndromic single malformations, such as split hand foot malformation (SHFM4) and isolated cleft lip (NSCL). In this article we will present an overview of diseases caused by mutations in the p63 gene and review the known pathogenic p63 gene mutations.

PRIMA-1MET/APR-246 targets mutant forms of p53 family members p63 and p73

“…These mutations in the p63 DNA-binding domain are associated with the EEC syndrome (Rinne et al, 2007). Western blotting revealed a robust increase in p63 protein expression on addition of doxycycline in all cell lines (Figures 3b and c, and data not shown).…”

p63 in epithelial development

“…p63 -/-mice also show truncated limbs and abnormal craniofacial development, due to failure to maintain or differentiate the apical ectodermal ridge, a structure which is important for coordination of epithelialmesenchymal interactions [4,5] and is required for limb outgrowth and palatal and facial structure formation. Second, mutations in the human p63 gene are responsible for ectodermal dysplastic syndromes [6,7]. But how does p63 contribute to the formation of the epidermis?…”

Mechanism of TAp73 inhibition by ΔNp63 and structural basis of p63/p73 hetero-tetramerization

“…5 Mutations in the human p63 gene are the cause for six different syndromes characterized by deformations of the limbs and/or skin erosions. 6,7 In tumors, however, mutations in the p63 gene are found only infrequently, suggesting that p63 is not a typical tumor suppressor. Overexpression of the ΔNp63α isoform, however, is observed in squamous cell carcinomas, particularly in head and neck squamous cell carcinomas (HNSCCs), a group of malignancies derived from cells of the basal epithelia of the aerodigestive mucosa.…”