Amino-terminal residues of ΔNp63, mutated in ectodermal dysplasia, are required for its transcriptional activity.

Anna Maria Lena, Sara Duca, Flavia Novelli, Sonia Melino, Margherita Annicchiarico-Petruzzelli, Gerry Melino, Eleonora Candi

Journal: Biochemical and biophysical research communications 2016;467(2):434-40

PMID: 26408908

Full Text on Elsevier Science View on PubMed

Abstract

p63, a member of the p53 family, is a crucial transcription factor for epithelial development and skin homeostasis. Heterozygous mutations in TP63 gene have been associated with human ectodermal dysplasia disorders. Most of these TP63 mutations are missense mutations causing amino acidic substitutions at p63 DNA binding or SAM domains that reduce or abolish the transcriptional activity of mutants p63. A significant number of mutants, however, resides in part of the p63 protein that apparently do not affect DNA binding and/or transcriptional activity, such as the N-terminal domain. Here, we characterize five p63 mutations at the 5' end of TP63 gene aiming to understand the pathogenesis of the diseases and to uncover the role of ΔNp63α N-terminus residues in determining its transactivation potential.

Address: Department of Experimental Medicine and Surgery, University of "Tor Vergata", Rome, Italy.; Department of Chemistry, University of "Tor Vergata", Rome, Italy.; IDI-IRCCS, Istituto Dermopatico dell'Immacolata, Biochemistry Laboratory, Rome, Italy.; Department of Experimental Medicine and Surgery, University of "Tor Vergata", Rome, Italy; MRC Toxicology Unit, Leicester, UK.; Department of Experimental Medicine and Surgery, University of "Tor Vergata", Rome, Italy; IDI-IRCCS, Istituto Dermopatico dell'Immacolata, Biochemistry Laboratory, Rome, Italy. Electronic address: [email protected].

DOI: 10.1016/j.bbrc.2015.09.111

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MeSH Terms: Amino Acid Sequence, Binding Sites, Carrier Proteins, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21, Cytoskeletal Proteins, Dystonin, Ectodermal Dysplasia, Genes, Reporter, HEK293 Cells, Humans, Keratin-14, Luciferases, Membrane Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Open Reading Frames, Protein Binding, Protein Precursors, Protein Structure, Tertiary, Recombinant Proteins, Response Elements, Sequence Deletion, Transcription Factors, Transcriptional Activation, Tumor Suppressor Proteins