Differential 9-cis-retinoic acid-dependent transcriptional activation by murine retinoid X receptor α (RXRα) and RXRβ: Role of cell type and RXR domains

Paul L. Hallenbeck, Saverio Minucci, Roland Lippoldt, Marcia Phyillaier, Valerie Horn, Keiko Ozato, Vera M. Nikodem

Research output: Contribution to journalArticlepeer-review

Abstract

The 9-cis-retinoic acid (9cRA)-inducible enhancer of the rat cellular retinol-binding protein type II gene (CRBP II) was shown to be differentially regulated by the murine retinoid X receptor α (RXRα) as compared with RXRβ. Transient transfection assays performed in NIH 3T3 fibroblast cells demonstrated that RXRα yielded a high level of 9cRA-dependent transcription of a reporter gene linked to the CRBP II enhancer, when compared with RXRβ. This effect was cell type-dependent, since both receptors elicited comparable transcriptional activation of the same reporter in P19 embryonal carcinoma cells. To further explore the structural determinants responsible for the differences between these two receptors, a series of chimeric receptor constructs were made. Co-transfection assays utilizing these chimeras demonstrated that both the N terminus and the hinge region connecting the DNA binding domain with the ligand binding domain of RXRα were responsible for the high level of 9cRA-dependent transcription observed in NIH 3T3 cells. Furthermore, the hinge region of RXRα was shown to be necessary to repress, in the absence of hormone, the transcriptional activation function located in the N-terminal domain of RXRα. These results stress the importance of functional links between different RXR domains and suggest an RXR subtype and cell type-dependent specificity in the control of the 9cRA response.

Original languageEnglish
Pages (from-to)10503-10507
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number18
DOIs
Publication statusPublished - 1996

ASJC Scopus subject areas

  • Biochemistry

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