Functional Interaction between Oct-1 and Retinoid X Receptor

• Published in: The Journal of biological chemistry Vol. 274; no. 27; pp. 19103 - 19108
• Main Authors: Kakizawa, Tomoko, Miyamoto, Takahide, Ichikawa, Kazuo, Kaneko, Atsuko, Suzuki, Satoru, Hara, Masahiro, Nagasawa, Takeshi, Takeda, Teiji, Mori, Jun-ichiro, Kumagai, Mieko, Hashizume, Kiyoshi
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 02.07.1999
• Subjects: Animals; Cell Line; COS Cells; DNA - metabolism; DNA-Binding Proteins - metabolism; Host Cell Factor C1; Humans; Octamer Transcription Factor-1; Octamer Transcription Factor-2; Rats; Receptors, Retinoic Acid - metabolism; Recombinant Fusion Proteins - metabolism; Retinoid X Receptors; Thyroid Hormones - metabolism; Transcription Factors - metabolism; Transcriptional Activation
• DOI: 10.1074/jbc.274.27.19103
• ISSN: 0021-9258

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.