Cross-talk between the NR3B and NR4A families of orphan nuclear receptors.
Estrogen-related receptors (NR3B family) and Nurr1, NGFI-B, and Nor1 (NR4A family) are orphan nuclear receptors lacking identified natural ligands. The mechanisms regulating their transcriptional activities have remained elusive. We have previously observed that the members of NR3B and NR4A families are coexpressed in certain cell types such as osteoblasts and that the ability of Nurr1 to transactivate the osteopontin promoter is repressed by ERRs. We have now studied the cross-talk between NR3B and NR4A receptors. We show that NR3B and NR4A receptors mutually repress each others' transcriptional activity. The repression involves intact DNA-binding domains and dimerization interfaces but does not result from competition for DNA binding or from heterodimerization. The activation functions of NR3B and NR4A receptors are dispensable for the cross-talk. In conclusion, we report that cross-talk between NR3B and NR4A receptors is a mechanism modulating the transcriptional activities of these orphan nuclear receptors.
Lammi
Johanna
J
Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Rajalin
Ann-Marie
AM
Huppunen
Johanna
J
Aarnisalo
Piia
P
D001667:Binding, Competitive; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D004967:Estrogens / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D053495:Osteopontin / Q000097:blood / Q000235:genetics; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D004967:Estrogens; D008024:Ligands; C501155:NR3B NMDA receptor; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D016194:Receptors, N-Methyl-D-Aspartate; D011987:Receptors, Steroid; D014157:Transcription Factors; D053495:Osteopontin; D004247:DNA