Title: Nuclear receptor transcriptional coactivators in development and metabolism
Abstract: This chapter discusses the role of nuclear receptor transcriptional coactivators in development and metabolism. The nuclear receptor superfamily in the human comprises 48 members that are ligand-regulated transcriptional factors and includes receptors for steroid and thyroid hormones, vitamin D3, retinoic acids, peroxisome proliferators, and others. Ligand-activated nuclear receptors regulate diverse biological processes, such as development, differentiation, neoplastic conversion, and several metabolic pathways, by controlling gene expression patterns in a cell- and gene-specific manner after binding to specific DNA sequences called “hormone responsive elements” located in the promoter regions of target genes. All nuclear receptors share a common structure with a highly conserved DNA-binding domain consisting of two zinc fingers, a C-terminal ligand (hormone)-binding domain, and two transcriptional-activation function (AF) domains termed AF-1 located in the N-terminal domain and AF-2 in the ligand-binding domain. While AF-1 functions in a ligand-independent manner, the transactivation of AF-2 domain is generally ligand dependent. Many of the unliganded nuclear receptors, including those for retinoid and thyroid hormone, are maintained mostly in the nucleus bound to DNA in a repressed state by nuclear receptor corepressors such as silencing mediator of retinoid and thyroid hormone receptors. Upon ligand binding, the corepressors dissociate from the nuclear receptor to commence transcription of target genes. Certain other nuclear receptors, such as glucocorticoid receptor (GR), require ligand binding to facilitate their translocation from the cytoplasm to the nucleus where the liganded receptor binds hormone responsive elements in DNA.
Publication Year: 2006
Publication Date: 2006-01-01
Language: en
Type: book-chapter
Indexed In: ['crossref']
Access and Citation
Cited By Count: 12
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