Generation of ΔTAp73 proteins by translation from a putative internal ribosome entry site

A. Emre Sayan, Jean Pierre Roperch, Berna S. Sayan, Mario Rossi, M. J. Pinkoski, Richard A. Knight, Anne E. Willis, Gerry Melino

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

p73 belongs to a family of transcription factors, including p53 and p63, that mediate response to DNA damage and cellular stress by inducing DNA repair, cell cycle arrest, and apoptosis. TP73 gene contains two promotors and several splice variants resulting in up to 24 possible permutations of p73 proteins which underlies the complexity of the family and its regulatory mechanisms. p73 variants lacking the N-terminal, denoted as ΔTAp73, are not transcriptionally competent and they act in a dominant negative fashion over TAp73. ΔTAp73 isoforms can be generated by alternative promotor usage, giving rise to ΔNp73, or alternative splicing of exons 2, 3 or 2, and 3 together. Such transcript isoforms potentially produce oncogenic proteins and they were shown to be present in primary tumors and tumor-derived cell lines. We investigated the possibility of additional mechanisms by which p73 protein could be regulated and discovered a putative internal ribosome entry site (IRES) in exon 2. Translation initiation of TAp73 mRNA results in a ΔNp73-like peptide, thus demonstrating an additional mechanism whereby a ΔTA p73 protein is produced from a transcript originally generated from the P1 promotor of the p73 gene.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
Pages315-324
Number of pages10
Volume1095
DOIs
Publication statusPublished - Jan 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1095
ISSN (Print)00778923
ISSN (Electronic)17496632

Keywords

  • IRES
  • p53 internal ribosome entry site
  • p73

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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