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Phosphorylated retinoid X receptor alpha loses its heterodimeric activity with retinoic acid receptor beta

Kotaro Yoshimura1, Yoshinori Muto, Masahito Shimizu

  • 1Department of Medicine, Gifu University Graduate School of Medicine, Gifu, 501-1194, Japan.

Cancer Science
|September 29, 2007
PubMed

Insights

Phosphorylation of retinoid X receptor (RXR) alpha disrupts its function, impairing cell growth control and promoting liver cancer. Inhibiting RXR alpha phosphorylation may offer a cancer treatment strategy.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cellular Signaling

Background:

  • Retinoid X receptor (RXR) alpha phosphorylation is linked to hepatocellular carcinoma development.
  • The exact mechanisms of phosphorylated RXR alpha dysfunction are not fully understood.

Purpose of the Study:

  • To investigate how RXR alpha phosphorylation affects its dimeric activity.
  • To explore the role of RXR alpha phosphorylation in liver cancer progression.

Main Methods:

  • Fluorescence resonance energy transfer (FRET) studies.
  • Immunoprecipitation assays.
  • Cell transfection with wild-type, phosphomimic, and unphosphorylated RXR alpha mutants.

Main Results:

  • Phosphorylation impaired RXR alpha interaction with retinoic acid receptor beta.
  • Unphosphorylated RXR alpha restored retinoid-induced transcriptional activity and apoptosis.
  • RXR alpha phosphorylation abolished dimerization, leading to loss of cell growth control and enhanced cancer cell growth.

Conclusions:

  • Phosphorylation of RXR alpha disrupts its homodimer and heterodimer formation, contributing to liver cancer.
  • Inhibiting RXR alpha phosphorylation could be a therapeutic strategy for cancer control.

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