Abstract
In this study we have demonstrated that dimerization of mammalian progesterone receptors (PR) occurs in the absence of DNA. A specific immune coisolation assay was performed on extracts of T-47D human breast cancer cells with a monoclonal antibody specific for the full-length B form of progesterone receptor (PR-B). This resulted in coisolation of significant amounts of truncated form-A receptors (PR-A), indicating the presence of stable PR-A·PR-B dimers in solution. A positive correlation was observed between the ability of different receptor forms to oligomerize in solution and their ability to bind to specific DNA sequences. The ability to form stable PR-A·PR-B oligomers in the absence of DNA was also found to correlate with release of 90-kDa heat shock protein (hsp90) from the unactivated PR complex. These results support the hypothesis that dimerization in the absence of DNA is an important mechanism controlling receptor DNA-binding function and that hsp90 release may be a key step regulating dimerization. This suggests that hsp90 may function to repress DNA-binding activity indirectly by blocking receptor dimerization.
Original language | English (US) |
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Pages (from-to) | 72-76 |
Number of pages | 5 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 88 |
Issue number | 1 |
DOIs | |
State | Published - 1991 |
Externally published | Yes |
Keywords
- DNA-binding protein
- dimers
- progesterone response elements
- steroid receptors
ASJC Scopus subject areas
- General