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Nuclear receptor coregulators: cellular and molecular biology
N J McKenna1, R B Lanz, B W O'Malley
1Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Endocrine Reviews
|June 16, 1999
Summary
Nuclear receptor coregulators, essential for gene regulation, act as coactivators or corepressors. These molecules modulate transcription rates by interacting with nuclear receptors, influencing gene expression.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Nuclear receptors require coregulators for effective transcriptional regulation.
- Coregulators function as coactivators (enhancing transcription) or corepressors (reducing transcription).
- They are typically rate-limiting for nuclear receptor activity but do not alter basal transcription significantly.
Purpose of the Study:
- To review the cellular and molecular biology of nuclear receptor coregulators.
- To highlight the diverse mechanisms of action for these regulatory molecules.
- To discuss their role in integrating signaling pathways at target gene promoters.
Main Methods:
- Literature review of recent data on nuclear receptor coregulators.
- Analysis of coregulator interactions with nuclear receptors and basal transcription factors.
- Examination of coregulator roles in histone modification and precomplex formation.
Main Results:
- Coregulators exhibit multiple modes of action, including direct interactions and covalent modifications.
- Many coregulators form precomplexes that assemble in promoter-specific configurations.
- Coregulators act as molecular gates, integrating diverse signal transduction pathways.
Conclusions:
- Nuclear receptor coregulators are critical for precise control of gene transcription.
- Their diverse functions and complex interactions underscore their importance in cellular regulation.
- Understanding coregulator biology is key to deciphering nuclear receptor-mediated signaling.
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