RGD Reference Report - Heterodimerization between members of the Nur subfamily of orphan nuclear receptors as a novel mechanism for gene activation. - Rat Genome Database

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Heterodimerization between members of the Nur subfamily of orphan nuclear receptors as a novel mechanism for gene activation.

Authors: Maira, M  Martens, C  Philips, A  Drouin, J 
Citation: Maira M, etal., Mol Cell Biol. 1999 Nov;19(11):7549-57.
RGD ID: 10054079
Pubmed: PMID:10523643   (View Abstract at PubMed)
PMCID: PMC84765   (View Article at PubMed Central)

We have recently shown that the orphan nuclear receptor Nur77 (NGFI-B) is most active in transcription when it is interacting with a cognate DNA sequence as a homodimer. Further, we have shown that the target for Nur77 dimers, the Nur response element (NurRE), is responsive to physiological stimuli in both endocrine and lymphoid cells, whereas other DNA targets of Nur77 action are not. The Nur77 subfamily also includes two related receptors, Nur-related factor 1 (Nurr1) and neuron-derived orphan receptor 1 (NOR-1). Often, more than one member of this subfamily is induced in response to extracellular signals. We now show that Nur77 and Nurr1 form heterodimers in vitro in the presence or absence of NurRE, and we have documented interactions between these proteins in vivo by using a two-hybrid system in mammalian cells. These heterodimers synergistically enhance transcription from NurRE reporters in comparison to that seen with homodimers. The naturally occurring NurRE from the pro-opiomelanocortin gene preferentially binds and activates transcription in the presence of Nur77 homo- or heterodimers, while a consensus NurRE sequence does not show this preference. Taken together, the data indicate that members of the Nur77 subfamily are most potent as heterodimers and that different dimers exhibit target sequence preference. Thus, we propose that a combinatorial code relying on specific NurRE sequences might be responsible for the activation of subsets of target genes by one of the members of the Nur77 subfamily of transcription factors.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of transcription by RNA polymerase II involved_inIDA 10054079PMID:10523643UniProt 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Nr4a1  (nuclear receptor subfamily 4, group A, member 1)
Nr4a3  (nuclear receptor subfamily 4, group A, member 3)


Additional Information