Retinol Increases beta-catenin-RXRalpha binding leading to the increased proteasomal degradation of beta-catenin and RXRalpha.
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.
Dillard
Alice C
AC
Department of Human Ecology, Division of Nutritional Sciences, The University of Texas at Austin, Austin, TX 78712, USA.
Lane
Michelle A
MA
D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014801:Vitamin A / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism*
D012333:RNA, Messenger; D047490:Retinoid X Receptor alpha; D014815:Vitamins; D051176:beta Catenin; D014801:Vitamin A