Induction of the Growth Inhibitor IGF-binding Protein 3 by p53

Nature. 1995 Oct 19;377(6550):646-9. doi: 10.1038/377646a0.

Abstract

Transcriptional activation of target genes represents an important component of the tumour-suppressor function of p53 and provides a functional link between p53 and various growth-regulatory processes, including cell cycle progression (p21/WAF1), DNA repair (GADD45) and apoptosis (bax). Here we use a differential cloning approach to identify the gene encoding insulin-like growth factor binding protein 3 (IGF-BP3) as a novel p53-regulated target gene. Induction of IGF-BP3 gene expression by wild-type but not mutant p53 is associated with enhanced secretion of an active form of IGF-BP3 capable of inhibiting mitogenic signalling by the insulin-like growth factor IGF-1. Our results indicate that IGF-BP3 may link p53 to potential novel autocrine/paracrine signalling pathways and to processes regulated by or dependent on IGF(s), such as cellular growth, transformation and survival.

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cell Division / physiology
  • Cell Line
  • Cloning, Molecular
  • DNA / metabolism
  • Doxorubicin / pharmacology
  • Gene Expression Regulation* / drug effects
  • Gene Expression Regulation* / physiology
  • Gene Expression Regulation* / radiation effects
  • Growth Inhibitors / biosynthesis
  • Growth Inhibitors / genetics*
  • Growth Inhibitors / metabolism
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / biosynthesis
  • Insulin-Like Growth Factor Binding Protein 3 / genetics*
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Insulin-Like Growth Factor I / antagonists & inhibitors
  • Molecular Sequence Data
  • Signal Transduction
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / physiology*
  • Ultraviolet Rays

Substances

  • Growth Inhibitors
  • Insulin-Like Growth Factor Binding Protein 3
  • Tumor Suppressor Protein p53
  • Insulin-Like Growth Factor I
  • Doxorubicin
  • DNA

Associated data

  • GENBANK/J05537