PMID: 16634145Apr 25, 2006Paper

Role of the mediator complex in nuclear hormone receptor signaling

Reviews of Physiology, Biochemistry and Pharmacology
Madesh Belakavadi, Joseph D Fondell

Abstract

Mediator is an evolutionarily conserved multisubunit protein complex that plays a key role in regulating transcription by RNA polymerase II. The complex functions by serving as a molecular bridge between DNA-bound transcriptional activators and the basal transcription apparatus. In humans, Mediator was first characterized as a thyroid hormone receptor (TR)-associated protein (TRAP) complex that facilitates ligand-dependent transcriptional activation by TR. More recently, Mediator has been established as an essential coactivator for a broad range of nuclear hormone receptors (NRs) as well as several other types of gene-specific transcriptional activators. A single subunit of the complex, MED1/TRAP220, is required for direct ligand-dependent interactions with NRs. Mediator coactivates NR-regulated gene expression by facilitating the recruitment and activation of the RNA polymerase II-associated basal transcription apparatus. Importantly, Mediator acts in concert with other NR coactivators involved in chromatin remodeling to initiate transcription of NR target genes in a multistep manner. In this review, we summarize the functional role of Mediator in NR signaling pathways with an emphasis on the underlying molecular mechanisms by...Continue Reading

Citations

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