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

doi:10.1016/j.bbrc.2015.09.111

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

Biochem Biophys Res Commun. 2015 Nov 13;467(2):434-40. doi: 10.1016/j.bbrc.2015.09.111. Epub 2015 Sep 25.

Authors

Anna Maria Lena¹, Sara Duca¹, Flavia Novelli¹, Sonia Melino², Margherita Annicchiarico-Petruzzelli³, Gerry Melino⁴, Eleonora Candi⁵

Affiliations

¹ Department of Experimental Medicine and Surgery, University of "Tor Vergata", Rome, Italy.
² Department of Chemistry, University of "Tor Vergata", Rome, Italy.
³ IDI-IRCCS, Istituto Dermopatico dell'Immacolata, Biochemistry Laboratory, Rome, Italy.
⁴ Department of Experimental Medicine and Surgery, University of "Tor Vergata", Rome, Italy; MRC Toxicology Unit, Leicester, UK.
⁵ 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].

PMID: 26408908
DOI: 10.1016/j.bbrc.2015.09.111

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.

Keywords: AEC; Ankyloblepharon-Ectodermal defects-cleft lip/palate syndrome; EEC; Ectodermal dysplasia; Ectrodactyly-Ectodermal dysplasia and cleft lip/palate syndrome; p53 family; p63.

MeSH terms

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

Substances

Carrier Proteins
Cyclin-Dependent Kinase Inhibitor p21
Cytoskeletal Proteins
DST protein, human
Dystonin
KRT14 protein, human
Keratin-14
Membrane Proteins
Nerve Tissue Proteins
Protein Precursors
Recombinant Proteins
TP63 protein, human
Transcription Factors
Tumor Suppressor Proteins
ZNF750 protein, human
envoplakin
Luciferases

Grants and funding

MC_U132670600/MRC_/Medical Research Council/United Kingdom