Differential ligand-dependent protein-protein interactions between nuclear receptors and a neuronal-specific cofactor

Greiner, E. F. and Kirfel, J. and Greschik, H. and Huang, D. and Becker, P. and Kapfhammer, J. P. and Schüle, R.. (2000) Differential ligand-dependent protein-protein interactions between nuclear receptors and a neuronal-specific cofactor. Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 13. pp. 7160-7165.

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Official URL: http://edoc.unibas.ch/dok/A5262200

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Nuclear receptors are transcription factors that require multiple protein-protein interactions to regulate target gene expression. We have cloned a 27-kDa protein, termed NIX1 (neuronal interacting factor X 1), that directly binds nuclear receptors in vitro and in vivo. Protein-protein interaction between NIX1 and ligand-activated or constitutive active nuclear receptors, including retinoid-related orphan receptor beta (RORbeta) (NR1F2), strictly depends on the conserved receptor C-terminal activation function 2 (AF2-D). NIX1 selectively binds retinoic acid receptor (RAR) (NR1A) and thyroid hormone receptor (TR) (NR1B) in a ligand-dependent manner, but does not interact with retinoid X receptor (RXR) (NR2B) or steroid hormone receptors. Interestingly, NIX1 down-regulates transcriptional activation by binding to ligand-bound nuclear receptors. A 39-aa domain within NIX1 was found to be necessary and sufficient for protein-protein interactions with nuclear receptors. Northern blot analysis demonstrates low-abundance RNA messages only in brain and neuronal cells. In situ hybridization and immunohistochemistry revealed that NIX1 expression is restricted to the central nervous system and could be confined to neurons in the dentate gyrus of the hippocampus, the amygdala, thalamic, and hypothalamic regions. In summary, protein-protein interactions between the neuronal protein NIX1 and ligand-activated nuclear receptors are both specific and selective. By suppressing receptor-mediated transcription, NIX1 implements coregulation of nuclear receptor functions in brain.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Anatomy > Developmental Neurobiology and Regeneration (Kapfhammer)
UniBasel Contributors:Kapfhammer, Josef
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:23
Deposited On:22 Mar 2012 13:34

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