Constitutive p63 expression in airway basal cells. A molecular target in diffuse lung diseases.
The p63 gene has high homology with p53, but more complex physiologic functions, including the regulation of the maintenance of basal cells in stratified epithelia. These cells in fact express high levels of the deltaN-terminal truncated isoforms of the p63 gene that can act as dominant-negative inhibiting the activity of p53. Basal cells in human bronchi and bronchioli seem to use the same strategy, since they constitutively express high levels of p63, at variance with alveolar pneumocytes. Over-expression of these isoforms in airway basal cells can inhibit important functions of the p53-pathway, including cell cycle arrest and apoptosis. This finding underlines the key role of p63 in epithelial renewal in human lung, with important implications in the understanding of the mechanisms of tissue remodelling occurring in diffuse lung diseases.
Chilosi
M
M
Department of Pathology, University of Verona, Italy. m.chilosi@univr.it
Doglioni
C
C
D017209:Apoptosis; D001980:Bronchi / Q000502:physiology*; D002453:Cell Cycle; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins; D016147:Genes, Tumor Suppressor; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000235:genetics / Q000503:physiopathology*; D008565:Membrane Proteins; D010750:Phosphoproteins / Q000096:biosynthesis*; D020545:Respiratory Mucosa / Q000166:cytology* / Q000502:physiology; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D018844:Cyclin-Dependent Kinases