title: Functional interaction between Oct-1 and retinoid X receptor.
abstract: The retinoid X receptor (RXR) is a member of the nuclear hormone receptor superfamily and heterodimerizes with a variety of other family members such as the thyroid hormone receptor (TR),1 retinoic acid receptor, vitamin D receptor, and peroxisome proliferator-activated receptor. Therefore, RXR is supposed to play a key role in a ligand-dependent regulation of gene transcription by nuclear receptors. In this study, we have identified the octamer-binding transcription factor-1 (Oct-1) as a novel interaction factor of RXR. In vitro pull-down assays using RXR deletion mutants showed that the interaction surfaces were located in the region encompassing the DNA binding domain (C domain) and the hinge domain (D domain) of RXR. We also showed that RXR interacted with the POU homeodomain but not with the POU-specific domain of Oct-1. Gel shift analysis revealed that Oct-1 reduced the binding of TR/RXR heterodimers to the thyroid hormone response element (TRE). In transient transfection assays using COS1 cells, Oct-1 repressed the T3-dependent transcriptional activity of TR/RXR heterodimers, consistent with in vitro DNA binding data; however, transcriptional activation by Gal4-TR(LBD) (LBD, ligand binding domain), which lacks its own DNA binding domain but retains responsiveness to T3, was not influenced by Oct-1. These results suggest that Oct-1 functionally interacts with RXR and negatively regulates the nuclear receptor signaling pathway by altering the DNA binding ability of the receptors.
authors.affiliation: Department of Geriatrics, Endocrinology, and Metabolism, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kakizawa
authors.forename: T
authors.initials: T
authors.lastname: Miyamoto
authors.forename: K
authors.initials: K
authors.lastname: Ichikawa
authors.forename: A
authors.initials: A
authors.lastname: Kaneko
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Hara
authors.forename: T
authors.initials: T
authors.lastname: Nagasawa
authors.forename: T
authors.initials: T
authors.lastname: Takeda
authors.forename: J i
authors.initials: Ji
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Kumagai
authors.forename: K
authors.initials: K
authors.lastname: Hashizume
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051863:Host Cell Factor C1; D006801:Humans; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D047488:Retinoid X Receptors; D013963:Thyroid Hormones / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; C494165:POU2F1 protein, human; C058435:POU2F2 protein, human; C494168:Pou2f1 protein, rat; C489205:Pou2f2 protein, rat; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D013963:Thyroid Hormones; D014157:Transcription Factors; D004247:DNA