Differential modulation of glucocorticoid and progesterone receptor transactivation.
The determinants of the different biological activities of progesterone receptors (PRs) vs. glucocorticoid receptors (GRs), which bind to the same DNA sequences, remain poorly understood. The mechanisms by which differential expression of a common target gene can be achieved by PR and GR include unequal agonist steroid concentrations for half maximal induction (EC50) and dissimilar amounts of residual partial agonist activity for antisteroids in addition to the more common changes in total gene induction, or Vmax. Several factors are known to alter some or all of these three parameters for GR-regulated gene induction and some (i.e., the corepressors NCoR and SMRT) modulate the EC50 and partial agonist activity for GR and PR induction of the same gene in opposite directions. The current study demonstrates that other factors known to modulate GR properties (GME, GMEB-2, Ubc9, and STAMP) can also differentially interact with PRs or alter several of the above induction parameters under otherwise identical conditions. These results support the hypothesis that the modulation of EC50, partial agonist activity, and Vmax by a given factor is not limited to one receptor in a specific cell line. Furthermore, the number of factors that unequally modulate PR and GR induction parameters is now greatly expanded, thereby increasing the possible mechanisms for differential gene regulation by PRs vs. GRs.
Szapary
Daniele
D
Steroid Hormones Section, NIDDK/CEB, National Institutes of Health, Bethesda, MD 20892-1772, United States.
Song
Liang-Nian
LN
He
Yuangzheng
Y
Simons
S Stoney
SS
D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism; D002522:Chlorocebus aethiops; D006801:Humans; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D011980:Receptors, Progesterone / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*; D020798:Two-Hybrid System Techniques; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D002352:Carrier Proteins; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D014157:Transcription Factors; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9