Selective receptor modulators, such as the antiprogestin RU486, are known to exhibit partial agonist activities in a cell-type-dependent manner. Employing an in vitro chromatin transcription system that recapitulates progesterone receptor (PR)-mediated transcription in vivo, we have investigated the molecular basis by which the antiprogestin RU486 regulates transcription in a cell-type-specific manner. We have compared the effects of RU486 on PR-dependent transcription in vitro using T47D and HeLa cell nuclear extracts. RU486 exhibits a differential ability to activate transcription within these two cell types. The differential effect on transcription correlates with different ratios of endogenous coactivators/corepressors in these cells. Unlike agonist-bound PR that interacts only with coactivators such as steroid receptor coactivator-1 (SRC-1), RU486-bound PR binds to both coactivator SRC-1 and corepressor silencing mediator for retinoid and thyroid hormone receptor (SMRT) in vitro. Both SRC-1 and SMRT have the capacity to modulate RU486-dependent activity. Moreover, a change in the relative levels of SRC-1 and SMRT contained in our chromatin transcription system modulates agonist/antagonist effects of RU486 on transcription by PR. Our data indicate that the ability of RU486 to activate transcription is modulated by the ratio of coactivators to corepressors and substantiate the important roles of coregulators in the regulation of steroid receptor mediated transactivation in response to selective receptor modulators.
Pharmacology, Toxicology and Pharmaceutical Science
2
5%
Other
4
11%
Unknown
9
24%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 November 2021.
All research outputs
#7,581,852
of 34,360,257 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#63,364
of 118,929 outputs
Outputs of similar age
#37,760
of 176,976 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#291
of 602 outputs
Altmetric has tracked 34,360,257 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 118,929 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 40.1. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 176,976 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.
We're also able to compare this research output to 602 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.
