p63 and IRF6: brothers in arms against cleft palate.
Cleft lip and cleft palate, which can also occur together as cleft lip and palate, are frequent and debilitating congenital malformations, with complex geneses that have both genetic and environmental factors implicated. Mutations in the genes encoding the p53 homolog p63 and interferon regulatory factor 6 (IRF6) are major causes of cleft lip and cleft palate, but the molecular and cellular mechanisms underlying this have not been clear. However, in this issue of the JCI, Thomason et al. and Moretti et al. independently show that p63 and IRF6 operate within a regulatory loop to coordinate epithelial proliferation and differentiation during normal palate development. Disruption of this loop as a result of mutations in p63 or IRF6 causes congenital clefting.
Gritli-Linde
Amel
A
Department of Oral Biochemistry, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden. amel@odontologi.gu.se
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002972:Cleft Palate / Q000196:embryology / Q000517:prevention & control* / Q000628:therapy; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D050835:Interferon Regulatory Factors / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D009154:Mutation; D010750:Phosphoproteins / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism
C081876:CKAP4 protein, human; C109803:IRF6 protein, human; C528250:IRF6 protein, mouse; D050835:Interferon Regulatory Factors; D008565:Membrane Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex