Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-alpha regulate transcriptional signaling and apoptosis

J Biol Chem. 2000 Oct 27;275(43):33607-13. doi: 10.1074/jbc.M002547200.

Abstract

Insulin-like growth factor-binding protein (IGFBP)-3 regulates apoptosis in an IGF-independent fashion and has been shown to localize to nuclei. We cloned the nuclear receptor retinoid X receptor-alpha(RXR-alpha) as an IGFBP-3 protein partner in a yeast two-hybrid screen. Multiple methodologies showed that IGFBP-3 and RXR-alpha bind each other within the nucleus. IGFBP-3-induced apoptosis was abolished in RXR-alpha-knockout cells. IGFBP-3 and RXR ligands were additive in inducing apoptosis in prostate cancer cells. IGFBP-3 enhanced RXR response element and inhibited RARE signaling. Thus, RXR-alpha-IGFBP-3 interaction leads to modulation of the transcriptional activity of RXR-alpha and is essential for mediating the effects of IGFBP-3 on apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • Binding Sites
  • COS Cells
  • Cloning, Molecular
  • Insulin-Like Growth Factor Binding Protein 3 / physiology*
  • Molecular Sequence Data
  • Receptors, Retinoic Acid / physiology*
  • Response Elements
  • Retinoid X Receptors
  • Transcription Factors / physiology*
  • Transcription, Genetic*

Substances

  • Insulin-Like Growth Factor Binding Protein 3
  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • Transcription Factors