Prostaglandin A2 Acts as a Transactivator for NOR1 (NR4A3) within the Nuclear Receptor Superfamily
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- Kagaya Shinji
- Genox Research Inc. Research Unit for Allergy Transcriptome, Research Center for Allergy & Immunology, RIKEN Yokohama Institute
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- Ohkura Naganari
- Tumor Endocrinology Project, National Cancer Center Research Institute, Japan
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- Tsukada Toshihiko
- Tumor Endocrinology Project, National Cancer Center Research Institute, Japan
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- Miyagawa Masami
- Genox Research Inc.
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- Sugita Yuji
- Genox Research Inc.
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- Tsujimoto Gozoh
- Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Matsumoto Kenji
- Department of Allergy and Immunology, National Research Institute for Child Health and Development, Japan
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- Saito Hirohisa
- Research Unit for Allergy Transcriptome, Research Center for Allergy & Immunology, RIKEN Yokohama Institute Department of Allergy and Immunology, National Research Institute for Child Health and Development, Japan
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- Hashida Ryoichi
- Genox Research Inc.
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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.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 28 (9), 1603-1607, 2005
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390282679602563328
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- NII Article ID
- 110003666475
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 7409417
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- PubMed
- 16141523
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed