Agonist-Occupied PRA Represses PRB via Interactions with Coactivators or Corepressors
Abstract
Hypothesis: the ability of agonist-occupied PRA (progesterone receptor A form) to act as a dominant negative inhibitor of many other receptors including progesterone receptor B form (PRB), ) is due to PRA's capacity to sequester away a common coactivator or recruit a common corepressor. Likely candidates for interaction include the coactivators SRC-l and TIF-2; corepressor candidates include NCoR and SMRT. Color variants of green fluorescent protein (GFP) were utilized for tagging PRA, PRB, SRC-l, TIF-2, NCoR, and SMRT. GFP-tagged proteins were then used in colocalization and confocal microscopy interaction studies. The purpose of this work was to find differential interactions between PRA and PRB and the above listed coactivators and corepressors. An extension of this project is cellular kinetic studies of drug-receptor complexes in living cells. The hypothesis of this part of the project was to correlate the rate of import into the nucleus of drug-occupied PRB with the dose of drug and hence the transcriptional activity of the drug. The global scope of this project was to better understand the precise roles of PRA and PRB with other cellular factors, as this is critical for finding better therapeutic targets and improved treatments for steroid-associated breast cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408993
Entities
People
- Carol S. Lim
Organizations
- University of Utah