Heterodimeric interaction between retinoid X receptor α and orphan nuclear receptor OR1 reveals dimerization-induced activation as a novel mechanism of nuclear receptor activation

Franziska F. Wiebel, Jan Åke Gustafsson

    Research output: Contribution to journalArticlepeer-review

    45 Scopus citations

    Abstract

    OR1 is a member of the steroid/thyroid hormone nuclear receptor superfamily which has been described to mediate transcriptional responses to retinoids and oxysterols. On a DR4 response element, an OR1 heterodimer with the nuclear receptor retinoid X receptor α (RXRα) has been described to convey transcriptional activation in both the absence and presence of the RXR ligand 9-cis retinoic acid, the mechanisms of which have remained unclear. Here, we dissect the effects of RXRα and OR1 ligand-binding domain interaction on transcriptional regulation and the role of the respective carboxy-terminal activation domains (AF-2s) in the absence and presence of the RXR ligand, employing chimeras of the nuclear receptors containing the heterologous GAL4 DNA-binding domain as well as natural receptors. The results show that the interaction of the RXR and OR1 ligand-binding domains unleashes a transcription activation potential that is mainly dependent on the AF-2 of OR1, indicating that interaction with RXR activates OR1. This defines dimerization-induced activation as a novel function of heterodimeric interaction and mechanism of receptor activation not previously described for nuclear receptors. Moreover, we present evidence that activation of OR1 occurs by a conformational change induced upon heterodimerization with RXR.

    Original languageEnglish (US)
    Pages (from-to)3977-3986
    Number of pages10
    JournalMolecular and Cellular Biology
    Volume17
    Issue number7
    DOIs
    StatePublished - Jul 1997

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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