Unliganded Thyroid Hormone Receptor- 1 Represses Liver X Receptor /Oxysterol-Dependent Transactivation

摘要: The thyroid hormone receptor (TR) and liver X (LXR)are members of the nuclear family are ligand-dependent transcription factors. Among promoter target genes, TR LXR recognize T3 response element (LXRE), respectively. Because elements LXREs have similar configurations, referred to as direct repeat 4, we investigated possibility cross-talk between two signal transduction pathways. We found that 1, a major isoform in liver, binds transactivates derived from mouse mammary tumor virus long-terminal sterol regulatory binding protein 1c. Moreover, unliganded 1 suppresses activity driven by its ligand, whereas transactivation T3-bound is not affected presence or absence oxysterols. Gel shift, mammalian twohybrid, glutathione S-transferase pull-down assays demonstrated these revealed interaction corepressors important TR-mediated suppression -transactivation. Our findings suggest influence lipid metabolism regulated oxysterol/LXR at transcriptional level. (Endocrinology 145: 5515–5524, 2004)