Abstract
Association of glucocorticoid (GR) and progesterone (PR) receptors with a set of molecular chaperones, including the 90-kDa heat shock protein (hsp90), is a dynamic process required for proper folding and maintaining these nuclear receptors under a transcriptionally inactive, ligand-responsive state. Mutational studies of the chicken hsp90 complementary DNA suggested that three regions of this protein (A, B, and Z) interact with the hormone-binding domain of GR, whereas region A is dispensable for hsp90 binding to PR. We found that this 69-amino acid region can be narrowed down to a 35-mer alpha-helical, acidic peptide, which is by itself able to inhibit hsp90 association to GR translated in vitro. The hsp90-free GR did not bind ligand, but was devoid of any specific DNA-binding activity, and higher peptide concentrations specifically inhibited the binding of activated GR to DNA. When overexpressed in cultured cells, this peptide acted as an antiglucocorticoid and inhibited the antiactivating protein-1 activity and the ligand-dependent nuclear transfer of GR. None of these effects, either in vivo and in vitro, was observed for PR. The region from residue 232 to residue 265 of hsp90 is, therefore, a domain critical for its assoc...Continue Reading
References
May 10, 1979·Nature·G G RousseauP Lustenberger
May 1, 1991·Molecular and Cellular Biology·P LefebvreG L Hager
Jan 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·A M DeMarzoD P Edwards
Nov 8, 1990·Nature·D PicardK R Yamamoto
Dec 17, 1987·Nature·V GiguereR M Evans
Feb 28, 1989·Biochemical and Biophysical Research Communications·N BinartM G Catelli
Dec 15, 1988·Nature·A Guiochon-MantelE Milgrom
Dec 27, 1988·Biochemistry·P LefebvreM Dautrevaux
Aug 21, 1987·Journal of Chromatography·B SablonniereM Dautrevaux
Jun 1, 1983·Cell·V L ChandlerK R Yamamoto
Dec 1, 1983·Cell·F PayvarK R Yamamoto
Nov 1, 1995·The Biochemical Journal·N BinartE E Baulieu
Aug 1, 1995·Proceedings of the National Academy of Sciences of the United States of America·S F Arnold, A C Notides
Oct 13, 1995·The Journal of Biological Chemistry·T W SchulteL Neckers
Aug 11, 1995·The Journal of Biological Chemistry·K A HutchisonW B Pratt
Sep 1, 1995·The Journal of Biological Chemistry·J K Owens-GrilloW B Pratt
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·M L WhitelawL Poellinger
Jun 2, 1995·Science·S P BohenK R Yamamoto
Jan 1, 1995·The Journal of Steroid Biochemistry and Molecular Biology·G AknerJ A Gustafsson
Nov 11, 1994·Nucleic Acids Research·J D ThompsonT J Gibson
Aug 15, 1994·Biochemical and Biophysical Research Communications·P CsermelyJ Somogyi
Jan 1, 1993·Annual Review of Genetics·D A Parsell, S Lindquist
Mar 1, 1994·The Journal of Steroid Biochemistry and Molecular Biology·F CadepondE E Baulieu
Dec 1, 1993·Molecular Endocrinology·A TahayatoM Dautrevaux
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·F CadepondE E Baulieu
Jan 4, 1994·Proceedings of the National Academy of Sciences of the United States of America·K I KangM G Catelli
Feb 1, 1993·Journal of Cellular Biochemistry·L P Freedman, B F Luisi
May 10, 1993·FEBS Letters·N TbarkaM Dautrevaux
Apr 1, 1993·The Journal of Steroid Biochemistry and Molecular Biology·K Dahlman-WrightJ Carlstedt-Duke
May 25, 1993·Biochemistry·L C ScherrerW B Pratt
Dec 1, 1995·Molecular and Cellular Biology·D F SmithR A Rimerman
Jun 7, 1996·The Journal of Biological Chemistry·J K Owens-GrilloW B Pratt
Citations
May 7, 1999·The Biochemical Journal·L SuaudB Laine
Dec 20, 2013·Cell and Tissue Research·Ellaine SalvadorCarola Förster
Jul 22, 2004·Annals of the New York Academy of Sciences·Salvatore AlesciIoannis Ilias
Dec 19, 2017·Frontiers in Physiology·Michael H LePamela K Den Besten
Apr 24, 2002·Pulmonary Pharmacology & Therapeutics·Shelby P UmlandSebastian L Johnston
Aug 8, 2021·Cells·Lorenz Weidenauer, Manfredo Quadroni