title: Mutations in the p53 homolog p63: allele-specific developmental syndromes in humans.
abstract: p63 is the most recently discovered but most ancient member of the p53 family. In marked contrast to p53, p63 is highly expressed in embryonic ectoderm and in the basal, regenerative layers of many epithelial tissues in the adult. The p63-knockout mouse dies at birth and lacks limbs, epidermis, prostate, breast and urothelial tissues, apparently owing to the loss of stem cells required for these tissues. Significantly, several dominant human syndromes involving limb development and/or ectodermal dysplasia have been mapped to chromosome 3q27 and ultimately the gene encoding p63. The heterozygous p63mutations are distinct for each of the syndromes and are thought to act through both dominant-negative and gain-of-function mechanisms rather than a loss-of-function haploinsufficiency. The allele specificity of these syndromes offers unique molecular insights into the poorly understood actions of p63 in limb development, ectodermal-mesodermal interactions and stem cell maintenance.
authors.affiliation: Dept of Human Genetics, University Medical Center Nijmegen, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: van Bokhoven
authors.forename: Frank
authors.initials: F
authors.lastname: McKeon
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000483:Alleles; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D016147:Genes, Tumor Suppressor; D006801:Humans; D008565:Membrane Proteins; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics*; D015398:Signal Transduction; D013577:Syndrome; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
chemical_list: C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C486419:Trp63 protein, mouse; D025521:Tumor Suppressor Proteins