ΔN-p63a and ta-p63a exhibit intrinsic differences in transactivation specificities that depend on distinct features of dna target sites

Paola Monti, Yari Ciribilli, Alessandra Bisio, Giorgia Foggetti, Ivan Raimondi, Paola Campomenosi, Paola Menichini, Gilberto Fronza, Alberto Inga

Research output: Contribution to journalArticle

Abstract

TP63 is a member of the TP53 gene family that encodes for up to ten different TA and ΔN isoforms through alternative promoter usage and alternative splicing. Besides being a master regulator of gene expression for squamous epithelial proliferation, differentiation and maintenance, P63, through differential expression of its isoforms, plays important roles in tumorigenesis. All P63 isoforms share an immunoglobulinlike folded DNA binding domain responsible for binding to sequence-specific response elements (REs), whose overall consensus sequence is similar to that of the canonical p53 RE. Using a defined assay in yeast, where P63 isoforms and RE sequences are the only variables, and gene expression assays in human cell lines, we demonstrated that human TA-and ΔN-P63a proteins exhibited differences in transactivation specificity not observed with the corresponding P73 or P53 protein isoforms. These differences 1) were dependent on specific features of the RE sequence, 2) could be related to intrinsic differences in their oligomeric state and cooperative DNA binding, and 3) appeared to be conserved in evolution. Since genotoxic stress can change relative ratio of TA-and ΔN-P63a protein levels, the different transactivation specificity of each P63 isoform could potentially influence cellular responses to specific stresses.

Original languageEnglish
Pages (from-to)2116-2130
Number of pages15
JournalOncotarget
Volume5
Issue number8
Publication statusPublished - 2014

Keywords

  • Response element
  • TP53
  • TP63
  • TP73
  • Transactivation specificity
  • Transcription

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

Fingerprint Dive into the research topics of 'ΔN-p63a and ta-p63a exhibit intrinsic differences in transactivation specificities that depend on distinct features of dna target sites'. Together they form a unique fingerprint.

  • Cite this

    Monti, P., Ciribilli, Y., Bisio, A., Foggetti, G., Raimondi, I., Campomenosi, P., Menichini, P., Fronza, G., & Inga, A. (2014). ΔN-p63a and ta-p63a exhibit intrinsic differences in transactivation specificities that depend on distinct features of dna target sites. Oncotarget, 5(8), 2116-2130.