title: Prostaglandin A2 acts as a transactivator for NOR1 (NR4A3) within the nuclear receptor superfamily.
abstract: Within the nuclear receptor superfamily, Nur77, Nurr1, and NOR1 constitute the nuclear receptor subfamily 4 group A. Modulation of NOR1 function would be therapeutic potential for diseases related to dysfunction of NOR1, including extraskeletal myxoid chondrosarcoma and autoimmune diseases. By screening arachidonate metabolites for their capacity of transcriptional activation, we have identified prostaglandin (PG) A2 as a transactivator for NOR1. PGA2 acted as a potent activator of NOR1-dependent transcription through the GAL4-based reporter system. The putative ligand-binding domain (LBD) of the receptor directly bound PGA2, and LBD-deleted receptor showed little transcriptional activation by PGA2. Primary cultured spleen cells derived from transgenic mice overexpressing NOR1, showed higher sensitivity to PGA2 compared to those from wild-type mice. These observations suggest that PGA2 can serve as a transactivator of NOR1, and thus suggest a possibility of pharmacological modulation of the NOR1 pathways by PGA2-related compounds.
authors.affiliation: Genox Research Inc., Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kagaya
authors.forename: Naganari
authors.initials: N
authors.lastname: Ohkura
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Tsukada
authors.forename: Masami
authors.initials: M
authors.lastname: Miyagawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sugita
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Hashida
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D006822:Hybrid Cells; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011454:Prostaglandins A / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D020349:Surface Plasmon Resonance; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C490411:Nr4a3 protein, mouse; D011454:Prostaglandins A; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D008156:Luciferases; D005982:Glutathione Transferase; C100008:prostaglandin A2