Wilms' tumour-suppressor protein isoforms have opposite effects on Igf2 expression in primary embryonic cells, independently of p53 genotype

Antonio Duarte, A A Caricasole, C F Graham, A Ward

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The p53 protein has been proposed as a modulator of the Wilms' tumour-suppressor protein (WT1) transcriptional regulation activity. To investigate this putative p53 role, the promoter P3 of the mouse insulin-like growth factor II gene (Igf2) was used as a target for WT1 regulation in primary cell cultures derived from p53 wild-type (p53+/+) and knock-out (p53-/-) mouse embryos. In these cells, the WT1 transcriptional activity was observed to be independent of p53 genotype. Furthermore, the two WT1 zinc finger (ZF) isoforms were for the first time found to have opposite effects on gene expression from a single promoter in the same cell type, WT1[-KTS] activating Igf2 P3, whereas WT1[+KTS] repressed its activity. In addition, we have mapped the WT1 binding sites and investigated the effect on WT1 binding activity of individual ZF deletions and Denys-Drash syndrome point mutations to this target.

Original languageEnglish
Pages (from-to)253-259
Number of pages7
JournalBritish Journal of Cancer
Volume77
Issue number2
Publication statusPublished - 1998

Keywords

  • Animals
  • Cells, Cultured
  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Gene Expression Regulation, Developmental
  • Genes, Wilms Tumor
  • Genes, p53
  • Genotype
  • Immediate-Early Proteins
  • Insulin-Like Growth Factor II
  • Mice
  • Mice, Knockout
  • Promoter Regions, Genetic
  • Transcription Factors
  • Transcription, Genetic
  • Transfection
  • WT1 Proteins
  • Journal Article
  • Research Support, Non-U.S. Gov't

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