Retinol Increases beta-catenin-RXRalpha binding leading to the increased proteasomal degradation of beta-catenin and RXRalpha

Nutr Cancer. 2008;60(1):97-108. doi: 10.1080/01635580701586754.


Retinol utilizes a retinoid X receptor (RXR)-mediated degradation pathway to decrease beta-catenin protein in all-trans retinoic acid (ATRA)-resistant human colon cancer cells. In this study, we examined interactions between RXRalpha and beta-catenin in ATRA-resistant human colon cancer cells treated with retinol. Retinol treatment triggers relocation of beta-catenin and RXRalpha proteins. Cells treated with retinol for 8 and 24 h displayed increased cytosolic but decreased nuclear beta-catenin and RXRalpha. Retinol treatment increased beta-catenin and RXRalpha protein interaction. Previously, we showed that 24 h of retinol treatment increased RXRalpha protein. Here we show this increase in RXRalpha levels is due to increased RXRalpha messenger RNA. Treatment with 48 h with retinol decreased RXRalpha protein levels. Last, by transfecting HCT-116 cells with a RXRalpha construct lacking the activation function-1 and DNA binding domains, we show RXRalpha and beta-catenin binding is required for proteosomal degradation of beta-catenin. These results suggest retinol induces RXRalpha and beta-catenin binding and transport to the cytosol where they are proteasomally degraded.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Colonic Neoplasms / metabolism*
  • Cytosol / metabolism
  • HCT116 Cells
  • Humans
  • Immunohistochemistry
  • Protein Binding
  • RNA, Messenger / metabolism
  • Retinoid X Receptor alpha / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vitamin A / pharmacology*
  • Vitamins / pharmacology*
  • beta Catenin / metabolism*


  • RNA, Messenger
  • Retinoid X Receptor alpha
  • Vitamins
  • beta Catenin
  • Vitamin A