Involvement of Nuclear Receptor Co-repressors in the Development of Human Breast Cancers
Abstract
All-trans retinoic acid (RA) inhibits proliferation of breast cancer cells, mediated by its nuclear receptor (RAR). In the absence of RA, the RAR represses basal transcription through direct interaction with SMRT (silencing mediator for retinoid and thyroid receptors) or N-CoR (nuclear receptor corepressor). In this project, we characterized receptor interaction and transcriptional repression mediated by SMRT and N-CoR. We investigated the expression and regulation of SMRT in breast cancer cells. We identified two nuclear receptor regions that are necessary for stable association with SMRT, and a C-terminus helix essential for ligand-dependent dissociation of the corepressor. SMRT and N-CoR contains two independent receptor interacting domains and multiple repressor sequences. We demonstrated that overexpression of SMRT enhanced transcriptional repression of nature RA-responsive promoters.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA383080
Entities
People
- J. D. Chen
Organizations
- University of Massachusetts