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PMID: 9398671 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Differential in vivo regulation of steroid hormone receptor activation by Cdc37p.

Molecular biology of the cell ·Vol. 8 ·No. 12 ·1997-12-00 ·Pages 2501-9

Fliss AE, Fang Y, Boschelli F, Caplan AJ

Abstract

The CDC37 gene is essential for the activity of p60(v-src) when expressed in yeast cells. Since the activation pathway for p60(v-src) and steroid hormone receptors is similar, the present study analyzed the hormone-dependent transactivation by androgen receptors and glucocorticoid receptors in yeast cells expressing a mutant version of the CDC37 gene. In this mutant, hormone-dependent transactivation by androgen receptors was defective at both permissive and restrictive temperatures, although transactivation by glucocorticoid receptors was mildly defective only at the restrictive temperature. Cdc37p appears to function via the androgen receptor ligand-binding domain, although it does not influence receptor hormone-binding affinity. Models for Cdc37p regulation of steroid hormone receptors are discussed.

MeSH Terms
Amino Acid Sequence Androgen Antagonists/metabolism,pharmacology Cell Cycle Proteins/chemistry,genetics,metabolism Chaperonins Desoxycorticosterone/metabolism,pharmacology Dihydrotestosterone/antagonists & inhibitors,metabolism,pharmacology Drosophila Proteins Flutamide/analogs & derivatives,metabolism,pharmacology Genes, Reporter/genetics Humans Ligands Molecular Chaperones Molecular Sequence Data Mutation/genetics Protein Structure, Tertiary Receptors, Androgen/genetics,metabolism Receptors, Glucocorticoid/genetics,metabolism Saccharomyces cerevisiae/drug effects,genetics Saccharomyces cerevisiae Proteins Temperature Thermodynamics Transcriptional Activation/drug effects
Chemicals
Androgen Antagonists CDC37 protein, S cerevisiae CDC37 protein, human Cell Cycle Proteins Drosophila Proteins Ligands Molecular Chaperones Receptors, Androgen Receptors, Glucocorticoid Saccharomyces cerevisiae Proteins Dihydrotestosterone hydroxyflutamide Desoxycorticosterone Flutamide Chaperonins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Fliss A E
Department of Cell Biology and Anatomy, Mount Sinai Medical Center, New York, New York 10029, USA.
Fang Y
Boschelli F
Caplan A J
References (42)
42 references, click to expand
  1. Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4.
    Genes Dev. 1996 Jun 15;10(12):1491-502 PMID: 8666233
  2. The lethality of p60v-src in Saccharomyces cerevisiae and the activation of p34CDC28 kinase are dependent on the integrity of the SH2 domain.
    J Cell Sci. 1993 Jun;105 ( Pt 2):519-28 PMID: 7691844
  3. A novel glycosaminoglycan-binding protein is the vertebrate homologue of the cell cycle control protein, Cdc37.
    J Biol Chem. 1995 Jul 7;270(27):16198-205 PMID: 7608185
  4. The KIN28 gene is required both for RNA polymerase II mediated transcription and phosphorylation of the Rpb1p CTD.
    J Mol Biol. 1995 Jun 9;249(3):535-44 PMID: 7783209
  5. Cdc37 is required for association of the protein kinase Cdc28 with G1 and mitotic cyclins.
    Proc Natl Acad Sci U S A. 1995 May 9;92(10):4651-5 PMID: 7753858
  6. Reconstitution of the multiprotein complex of pp60src, hsp90, and p50 in a cell-free system.
    J Biol Chem. 1992 Feb 15;267(5):2902-8 PMID: 1310678
  7. Physical interaction of mammalian CDC37 with CDK4.
    J Biol Chem. 1996 Sep 6;271(36):22030-4 PMID: 8703009
  8. Studies on the transformation of intact yeast cells by the LiAc/SS-DNA/PEG procedure.
    Yeast. 1995 Apr 15;11(4):355-60 PMID: 7785336
  9. Changes in the abundance of androgen receptor isotypes: effects of ligand treatment, glutamine-stretch variation, and mutation of putative phosphorylation sites.
    Biochemistry. 1994 Nov 29;33(47):14064-72 PMID: 7947816
  10. Characterization of response elements for androgens, glucocorticoids and progestins in mouse mammary tumour virus.
    Nucleic Acids Res. 1988 Jun 24;16(12):5263-76 PMID: 2838812
  11. Hsp90 regulates androgen receptor hormone binding affinity in vivo.
    J Biol Chem. 1996 Nov 8;271(45):28697-702 PMID: 8910505
  12. Mutational analysis of Hsp90 function: interactions with a steroid receptor and a protein kinase.
    Mol Cell Biol. 1995 Jul;15(7):3917-25 PMID: 7791797
  13. A 50 kilodalton protein associated with raf and pp60(v-src) protein kinases is a mammalian homolog of the cell cycle control protein cdc37.
    Biochemistry. 1997 Mar 25;36(12):3600-7 PMID: 9132011
  14. Disruption of the Raf-1-Hsp90 molecular complex results in destabilization of Raf-1 and loss of Raf-1-Ras association.
    J Biol Chem. 1995 Oct 13;270(41):24585-8 PMID: 7592678
  15. Cdc37 is a molecular chaperone with specific functions in signal transduction.
    Genes Dev. 1997 Jul 15;11(14):1775-85 PMID: 9242486
  16. A pathway of multi-chaperone interactions common to diverse regulatory proteins: estrogen receptor, Fes tyrosine kinase, heat shock transcription factor Hsf1, and the aryl hydrocarbon receptor.
    Cell Stress Chaperones. 1996 Dec;1(4):237-50 PMID: 9222609
  17. Binding of p23 and hsp90 during assembly with the progesterone receptor.
    Mol Endocrinol. 1995 Jun;9(6):670-8 PMID: 8592513
  18. Cdc37: a protein kinase chaperone?
    Trends Cell Biol. 1997 Apr;7(4):157-61 PMID: 17708934
  19. Elevated recombination rates in transcriptionally active DNA.
    Cell. 1989 Feb 24;56(4):619-30 PMID: 2645056
  20. Progesterone receptor structure and function altered by geldanamycin, an hsp90-binding agent.
    Mol Cell Biol. 1995 Dec;15(12):6804-12 PMID: 8524246
  21. The yeast CDC37 gene interacts with MPS1 and is required for proper execution of spindle pole body duplication.
    J Cell Biol. 1997 Mar 10;136(5):969-82 PMID: 9060463
  22. Interaction of the Rous sarcoma virus protein pp60src with the cellular proteins pp50 and pp90.
    Curr Top Microbiol Immunol. 1986;123:1-22 PMID: 2419040
  23. Raf exists in a native heterocomplex with hsp90 and p50 that can be reconstituted in a cell-free system.
    J Biol Chem. 1993 Oct 15;268(29):21711-6 PMID: 8408024
  24. Assembly of progesterone receptor with heat shock proteins and receptor activation are ATP mediated events.
    J Biol Chem. 1992 Jan 15;267(2):1350-6 PMID: 1730655
  25. Yeast molecular chaperones and the mechanism of steroid hormone action.
    Trends Endocrinol Metab. 1997 Sep;8(7):271-5 PMID: 18406815
  26. Proof that hsp70 is required for assembly of the glucocorticoid receptor into a heterocomplex with hsp90.
    J Biol Chem. 1994 Feb 18;269(7):5043-9 PMID: 8106480
  27. An androgen-inducible expression system for Saccharomyces cerevisiae.
    Gene. 1991 Sep 30;106(1):35-42 PMID: 1937039
  28. The Ydj1 molecular chaperone facilitates formation of active p60v-src in yeast.
    Mol Biol Cell. 1996 Jan;7(1):91-100 PMID: 8741842
  29. Evidence that the 90-kDa heat shock protein (HSP90) exists in cytosol in heteromeric complexes containing HSP70 and three other proteins with Mr of 63,000, 56,000, and 50,000.
    J Biol Chem. 1991 Apr 15;266(11):6708-13 PMID: 2016286
  30. Identification of three proline-directed phosphorylation sites in the human androgen receptor.
    Mol Endocrinol. 1995 May;9(5):605-15 PMID: 7565807
  31. Mutations in Hsp83 and cdc37 impair signaling by the sevenless receptor tyrosine kinase in Drosophila.
    Cell. 1994 Jul 1;77(7):1027-36 PMID: 8020093
  32. A 50-kDa cytosolic protein complexed with the 90-kDa heat shock protein (hsp90) is the same protein complexed with pp60v-src hsp90 in cells transformed by the Rous sarcoma virus.
    J Biol Chem. 1991 Sep 5;266(25):16436-40 PMID: 1653236
  33. Aberrant protein phosphorylation at tyrosine is responsible for the growth-inhibitory action of pp60v-src expressed in the yeast Saccharomyces cerevisiae.
    Mol Biol Cell. 1994 Mar;5(3):283-96 PMID: 8049521
  34. Role of the protein chaperone YDJ1 in establishing Hsp90-mediated signal transduction pathways.
    Science. 1995 Jun 2;268(5215):1362-5 PMID: 7761857
  35. Hormone-dependent transactivation by the human androgen receptor is regulated by a dnaJ protein.
    J Biol Chem. 1995 Mar 10;270(10):5251-7 PMID: 7890635
  36. Dynamics of heat shock protein 90-progesterone receptor binding and the disactivation loop model for steroid receptor complexes.
    Mol Endocrinol. 1993 Nov;7(11):1418-29 PMID: 7906860
  37. Mammalian glucocorticoid receptor derivatives enhance transcription in yeast.
    Science. 1988 Aug 19;241(4868):965-7 PMID: 3043665
  38. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation.
    Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8324-8 PMID: 8078881
  39. Interaction of the 90-kDa heat shock protein with native and in vitro translated androgen receptor and receptor fragments.
    Mol Cell Endocrinol. 1992 Oct;88(1-3):165-74 PMID: 1459337
  40. CDC37 is required for p60v-src activity in yeast.
    Mol Biol Cell. 1996 Sep;7(9):1405-17 PMID: 8885235
  41. Activation of the human androgen receptor through a protein kinase A signaling pathway.
    J Biol Chem. 1996 Aug 16;271(33):19900-7 PMID: 8702703
  42. Hold 'em and fold 'em: chaperones and signal transduction.
    Science. 1995 Jun 2;268(5215):1303-4 PMID: 7761850
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.8.12.2501
Published
1997-12-00
Pages
2501-9
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC25723
Subset
IM
Grants
NIDDK NIH HHS · R01 DK-49065 · United States
External Links
PubMed source DOI: 10.1091/mbc.8.12.2501 PMC Full Text View journal details
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