| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Biology Program (V.G.T., S.K.N.), Department of Pathology (S.K.N.), University of Colorado Health Sciences Center, Denver, Colorado 80262; and Department of Biochemistry and Molecular Biology (D.O.T.), Mayo Graduate School, Rochester, Minnesota 55905
Address all correspondence and requests for reprints to: Steven Nordeen, Department of Pathology B216, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado 80262. E-mail: Steve.Nordeen{at}UCHSC.edu.
To elucidate the earliest molecular steps in the activation of transcription by the progesterone receptor (PR), we investigated its activity in a cell-free transcription system utilizing chromatin templates. PR prepared as a ligand-free, recombinant protein failed to induce transcription on chromatin templates. However, transcriptional competence could be restored by coincubation with rabbit reticulocyte lysate (RRL). The interaction of PR with chaperones results in a receptor conformation competent to bind ligand and RRL contains abundant chaperone-mediated protein folding activity. Blocking this activity with the specific inhibitor geldanamycin inhibited receptor-dependent transcriptional activity. However, recombinant chaperones could not replace RRL in the restoration of transcriptional activity on chromatin templates, suggesting the presence of an additional activity in the lysate. Under chromatin assembly conditions, PR could bind naked DNA and RRL did not increase that binding. In contrast, PR bound to a chromatin template only poorly. Interestingly, RRL stimulated sequence-specific binding by PR to target sites in chromatin and the concomitant recruitment of the steroid receptor coactivator 1 to the promoter. Thus, our results indicate that a novel protein-mediated activity in RRL is involved in an additional, heretofore unrecognized, activation step required for PR to become transcriptionally competent on chromatin templates.
NURSA Molecule Pages Link:
This article has been cited by other articles:
 |
|
 |
|
  D. F. Smith and D. O. Toft Minireview: The Intersection of Steroid Receptors with Molecular Chaperones: Observations and Questions Mol. Endocrinol., October 1, 2008; 22(10): 2229 - 2240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Feng, P. Yi, J. Wong, and B. W. O'Malley Signaling within a Coactivator Complex: Methylation of SRC-3/AIB1 Is a Molecular Switch for Complex Disassembly Mol. Cell. Biol., November 1, 2006; 26(21): 7846 - 7857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. G. Thackray, S. M. McGillivray, and P. L. Mellon Androgens, Progestins, and Glucocorticoids Induce Follicle-Stimulating Hormone {beta}-Subunit Gene Expression at the Level of the Gonadotrope Mol. Endocrinol., September 1, 2006; 20(9): 2062 - 2079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Dilworth, K. J. Seaver, A. L. Fishburn, S. L. Htet, and S. J. Tapscott In vitro transcription system delineates the distinct roles of the coactivators pCAF and p300 during MyoD/E47-dependent transactivation PNAS, August 10, 2004; 101(32): 11593 - 11598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Nelson, V. Prapapanich, P. E. Carrigan, P. J. Roberts, D. L. Riggs, and D. F. Smith The Heat Shock Protein 70 Cochaperone Hip Enhances Functional Maturation of Glucocorticoid Receptor Mol. Endocrinol., July 1, 2004; 18(7): 1620 - 1630. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
