Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently

Mark Leid, Philippe Kastner, Ruth Lyons, Harikrishna Nakshatri, Michael Saunders, Tim Zacharewski, Jia Yang Chen, Adrien Staub, Jean Marie Garnier, Sylvie Mader, Pierre Chambon

Research output: Contribution to journalArticle

982 Scopus citations

Abstract

We have purified and cloned a HeLa cell nuclear protein that strongly stimulates binding of retinoic acid and thyroid hormone receptors (RARs and TRs) to response elements. The purified protein is a human retinoid X receptor β (hRXRβ). Three murine members of the RXR family (mRXRα, β, and γ) have also been cloned, and their interactions with RARs and TRs have been investigated. Under conditions where RAR, RXR, and TR bound poorly as homodimers to various response elements, strongly cooperative RAR-RXR and TR-RXR binding was observed. The binding efficiency was dependent on the sequence, relative orientation, and spacing of the repeated motifs of response elements. We show also that unstable RAR-RXR heterodimers were formed in solution, and that C-terminal sequences and the DNA-binding domains of both receptors were required for efficient formation of stable heterodimers on response elements. These findings suggest a convergence of the signaling pathways of some members of the nuclear receptor superfamily.

Original languageEnglish (US)
Pages (from-to)377-395
Number of pages19
JournalCell
Volume68
Issue number2
DOIs
StatePublished - Jan 24 1992
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Leid, M., Kastner, P., Lyons, R., Nakshatri, H., Saunders, M., Zacharewski, T., Chen, J. Y., Staub, A., Garnier, J. M., Mader, S., & Chambon, P. (1992). Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell, 68(2), 377-395. https://doi.org/10.1016/0092-8674(92)90478-U