2. Academic Validation
  3. Rosiglitazone binds to RXRα to induce RXRα tetramerization and NB4 cell differentiation

Rosiglitazone binds to RXRα to induce RXRα tetramerization and NB4 cell differentiation

  • Biochem Biophys Res Commun. 2020 Sep 10;530(1):160-166. doi: 10.1016/j.bbrc.2020.06.134.
Fengyu Huang 1,  Yihuan Li 1,  Junjie Chen 2,  Xiao-Kun Zhang 2,  Hu Zhou 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian, 361102, China.
  • 2 School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian, 361102, China; High Throughput Drug Screening Platform, Xiamen University, Xiamen, Fujian, 361102, China.
  • 3 School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian, 361102, China; High Throughput Drug Screening Platform, Xiamen University, Xiamen, Fujian, 361102, China. Electronic address: huzhou@xmu.edu.cn.
PMID: 32828280 DOI: 10.1016/j.bbrc.2020.06.134
Abstract

Rosiglitazone is a ligand of peroxisome proliferation-activated receptor gamma (PPARγ). However, it exerts biological activities and therapeutic effects through both PPARγ-dependent and independent mechanisms. In this study, we defined that rosiglitazone was also a ligand of retinoid X receptor alpha (RXRα) and displayed RXRα-dependent activities. We found that rosiglitazone directly bound to the ligand binding domain (LBD) of RXRα and induced RXRα/LBD tetramerization. Rosiglitazone inhibited the agonist-induced transcriptional activity of RXRα homodimers and heterodimers likely through inhibiting RXRα homo- and hetero-dimerization. In acute promyelocytic leukemia (APL) NB4 cells, rosiglitazone inhibited cell proliferation and induced cell differentiation, resulting from inhibiting RXRα/PML-RARα complex formation and down-regulating PML-RARα. Together, our study identified RXRα as a novel target of rosiglitazone and RXRα mediating the anti-APL activity of rosiglitazone.

Keywords

Acute promyelocytic leukemia; PML-RARα; Peroxisome proliferation-activated receptor gamma; Retinoid X receptor alpha; Rosiglitazone.

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