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Nuclear receptor coactivators: structural and functional biochemistry.

ABSTRACT: Transcription of eukaryotic cell is a multistep process tightly controlled by concerted action of macromolecules. Nuclear receptors are ligand-activated sequence-specific transcription factors that bind DNA and activate (or repress) transcription of specific sets of nuclear target genes. Successful activation of transcription by nuclear receptors and most other transcription factors requires "coregulators" of transcription. Coregulators make up a diverse family of proteins that physically interact with and modulate the activity of transcription factors and other components of the gene expression machinery via multiple biochemical mechanisms. The coregulators include coactivators that accomplish reactions required for activation of transcription and corepressors that suppress transcription. This review summarizes our current knowledge of nuclear receptor coactivators with an emphasis on their biochemical mechanisms of action and means of regulation.

SUBMITTER: Bulynko YA

PROVIDER: S-EPMC3647688 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Nuclear receptor coactivators: structural and functional biochemistry.

Bulynko Yaroslava A YA O'Malley Bert W BW

Biochemistry 20101229 3

Transcription of eukaryotic cell is a multistep process tightly controlled by concerted action of macromolecules. Nuclear receptors are ligand-activated sequence-specific transcription factors that bind DNA and activate (or repress) transcription of specific sets of nuclear target genes. Successful activation of transcription by nuclear receptors and most other transcription factors requires "coregulators" of transcription. Coregulators make up a diverse family of proteins that physically intera ...[more]

PMID: 21141906

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Project description:Background/aimsThe steroid hormones, including estradiol (E) and progesterone, act in the brain to regulate female reproductive behavior and physiology. These hormones mediate many of their biological effects by binding to their respective intracellular receptors. The receptors for estrogens (ER) and progestins (PR) interact with nuclear receptor coactivators to initiate transcription of steroid-responsive genes. Work from our laboratory and others reveals that nuclear receptor coactivators, including steroid receptor coactivator-1 (SRC-1) and SRC-2, function in brain to modulate ER-mediated induction of the PR gene and hormone-dependent behaviors. In order for steroid receptors and coactivators to function together, both must be expressed in the same cells.MethodsTriple-label immunofluorescence was used to determine if E-induced PR cells also express SRC-1 or SRC-2 in reproductively relevant brain regions of the female mouse.ResultsThe majority of E-induced PR cells in the medial preoptic area (61%), ventromedial nucleus of the hypothalamus (63%) and arcuate nucleus (76%) coexpressed both SRC-1 and SRC-2. A smaller proportion of PR cells expressed either SRC-1 or SRC-2, while a few PR cells expressed neither coactivator. In addition, compared to control animals, 17β-estradiol benzoate (EB) treatment increased SRC-1 levels in the arcuate nucleus, but not the medial preoptic area or the ventromedial nucleus of the hypothalamus. EB did not alter SRC-2 expression in any of the three brain regions analyzed.ConclusionsTaken together, the present findings identify a population of cells in which steroid receptors and nuclear receptor coactivators may interact to modulate steroid sensitivity in brain and regulate hormone-dependent behaviors in female mice. Given that cell culture studies reveal that SRC-1 and SRC-2 can mediate distinct steroid-signaling pathways, the present findings suggest that steroids can produce a variety of complex responses in these specialized brain cells.

Dataset Information

Nuclear receptor coactivators: structural and functional biochemistry.

Publications

Nuclear receptor coactivators: structural and functional biochemistry.

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