Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 6 December 1996:
Vol. 274. no. 5293, pp. 1713 - 1715
DOI: 10.1126/science.274.5293.1713
Prev | Table of Contents | Next

Reports

A Cyclophilin Function in Hsp90-Dependent Signal Transduction

Andrea A. Duina, * Hui-Chen Jane Chang, * James A. Marsh, Susan Lindquist, Richard F. Gaber dagger

Cpr6 and Cpr7, the Saccharomyces cerevisiae homologs of cyclophilin-40 (CyP-40), were shown to form complexes with Hsp90, a protein chaperone that functions in several signal transduction pathways. Deletion of CPR7 caused severe growth defects when combined with mutations that decrease the amount of Hsp90 or Sti1, another component of the Hsp90 chaperone machinery. The activities of two heterologous Hsp90-dependent signal transducers expressed in yeast, glucocorticoid receptor and pp60v-src kinase, were adversely affected by cpr7 null mutations. These results suggest that CyP-40 cyclophilins play a general role in Hsp90-dependent signal transduction pathways under normal growth conditions.

A. A. Duina, J. A. Marsh, R. F. Gaber, Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2153 Sheridan Road, Evanston, IL 60208, USA .
H.-C. J. Chang and S. Lindquist, Howard Hughes Medical Institute, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed.

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Cyclophilin 40 is required for microRNA activity in Arabidopsis.
M. R. Smith, M. R. Willmann, G. Wu, T. Z. Berardini, B. Moller, D. Weijers, and R. S. Poethig (2009)
PNAS 106, 5424-5429
   Abstract »    Full Text »    PDF »
Silencing of HSP90 Cochaperone AHA1 Expression Decreases Client Protein Activation and Increases Cellular Sensitivity to the HSP90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin.
J. L. Holmes, S. Y. Sharp, S. Hobbs, and P. Workman (2008)
Cancer Res. 68, 1188-1197
   Abstract »    Full Text »    PDF »
The Immunophilin Ligands Cyclosporin A and FK506 Suppress Prostate Cancer Cell Growth by Androgen Receptor-Dependent and -Independent Mechanisms.
S. Periyasamy, M. Warrier, M. P. M. Tillekeratne, W. Shou, and E. R. Sanchez (2007)
Endocrinology 148, 4716-4726
   Abstract »    Full Text »    PDF »
Sgt1p Is a Unique Co-chaperone That Acts as a Client Adaptor to Link Hsp90 to Skp1p.
M. G. Catlett and K. B. Kaplan (2006)
J. Biol. Chem. 281, 33739-33748
   Abstract »    Full Text »    PDF »
Independent Regulation of Hsp70 and Hsp90 Chaperones by Hsp70/Hsp90-organizing Protein Sti1 (Hop1).
Y. Song and D. C. Masison (2005)
J. Biol. Chem. 280, 34178-34185
   Abstract »    Full Text »    PDF »
Cyclophilin A Is Localized to the Nucleus and Controls Meiosis in Saccharomyces cerevisiae.
M. Arevalo-Rodriguez and J. Heitman (2005)
Eukaryot. Cell 4, 17-29
   Abstract »    Full Text »    PDF »
FKBP12 Controls Aspartate Pathway Flux in Saccharomyces cerevisiae To Prevent Toxic Intermediate Accumulation.
M. Arevalo-Rodriguez, X. Pan, J. D. Boeke, and J. Heitman (2004)
Eukaryot. Cell 3, 1287-1296
   Abstract »    Full Text »    PDF »
Cns1 Is an Activator of the Ssa1 ATPase Activity.
O. Hainzl, H. Wegele, K. Richter, and J. Buchner (2004)
J. Biol. Chem. 279, 23267-23273
   Abstract »    Full Text »    PDF »
Sti1 and Cdc37 Can Stabilize Hsp90 in Chaperone Complexes with a Protein Kinase.
P. Lee, A. Shabbir, C. Cardozo, and A. J. Caplan (2004)
Mol. Biol. Cell 15, 1785-1792
   Abstract »    Full Text »    PDF »
The Arabidopsis Cyclophilin Gene Family.
P. G.N. Romano, P. Horton, and J. E. Gray (2004)
Plant Physiology 134, 1268-1282
   Abstract »    Full Text »    PDF »
Lessons from the Genome Sequence of Neurospora crassa: Tracing the Path from Genomic Blueprint to Multicellular Organism.
K. A. Borkovich, L. A. Alex, O. Yarden, M. Freitag, G. E. Turner, N. D. Read, S. Seiler, D. Bell-Pedersen, J. Paietta, N. Plesofsky, et al. (2004)
Microbiol. Mol. Biol. Rev. 68, 1-108
   Abstract »    Full Text »    PDF »
Differential Expression of Pine and Cronartium quercuum f. sp. fusiforme Genes in Fusiform Rust Galls.
J. M. Warren and S. F. Covert (2004)
Appl. Envir. Microbiol. 70, 441-451
   Abstract »    Full Text »    PDF »
The Hsp90 Molecular Chaperone Complex Regulates Maltose Induction and Stability of the Saccharomyces MAL Gene Transcription Activator Mal63p.
M. Bali, B. Zhang, K. A. Morano, and C. A. Michels (2003)
J. Biol. Chem. 278, 47441-47448
   Abstract »    Full Text »    PDF »
Functional Interactions between Hsp90 and the Co-chaperones Cns1 and Cpr7 in Saccharomyces cerevisiae.
M. Tesic, J. A. Marsh, S. B. Cullinan, and R. F. Gaber (2003)
J. Biol. Chem. 278, 32692-32701
   Abstract »    Full Text »    PDF »
Aha1 Binds to the Middle Domain of Hsp90, Contributes to Client Protein Activation, and Stimulates the ATPase Activity of the Molecular Chaperone.
G. P. Lotz, H. Lin, A. Harst, and W. M. J. Obermann (2003)
J. Biol. Chem. 278, 17228-17235
   Abstract »    Full Text »    PDF »
Regulation of Signaling Protein Function and Trafficking by the hsp90/hsp70-Based Chaperone Machinery.
W. B. Pratt and D. O. Toft (2003)
Experimental Biology and Medicine 228, 111-133
   Abstract »    Full Text »    PDF »
Chaperoning signaling pathways: molecular chaperones as stress-sensing `heat shock' proteins.
E. A. A. Nollen and R. I. Morimoto (2002)
J. Cell Sci. 115, 2809-2816
   Abstract »    Full Text »    PDF »
Role of p50/CDC37 in Hepadnavirus Assembly and Replication.
X. Wang, N. Grammatikakis, and J. Hu (2002)
J. Biol. Chem. 277, 24361-24367
   Abstract »    Full Text »    PDF »
The Agonist Activity of Tamoxifen Is Inhibited by the Short Heterodimer Partner Orphan Nuclear Receptor in Human Endometrial Cancer Cells.
C. M. Klinge, S. C. Jernigan, and K. E. Risinger (2002)
Endocrinology 143, 853-867
   Abstract »    Full Text »    PDF »
Identification and Characterization of ART-27, a Novel Coactivator for the Androgen Receptor N Terminus.
S. M. Markus, S. S. Taneja, S. K. Logan, W. Li, S. Ha, A. B. Hittelman, I. Rogatsky, and M. J. Garabedian (2002)
Mol. Biol. Cell 13, 670-682
   Abstract »    Full Text »    PDF »
Cyclophilin A Mediates Vid22p Function in the Import of Fructose-1,6-bisphosphatase into Vid Vesicles.
C. R. Brown, D.-Y. Cui, G. G.-C. Hung, and H.-L. Chiang (2001)
J. Biol. Chem. 276, 48017-48026
   Abstract »    Full Text »    PDF »
Hsp104 Interacts with Hsp90 Cochaperones in Respiring Yeast.
T. Abbas-Terki, O. Donze, P.-A. Briand, and D. Picard (2001)
Mol. Cell. Biol. 21, 7569-7575
   Abstract »    Full Text »    PDF »
Protein Interactions of the MLL PHD Fingers Modulate MLL Target Gene Regulation in Human Cells.
K. Fair, M. Anderson, E. Bulanova, H. Mi, M. Tropschug, and M. O. Diaz (2001)
Mol. Cell. Biol. 21, 3589-3597
   Abstract »    Full Text »
Regulation of Vegetative Phase Change in Arabidopsis thaliana by Cyclophilin 40.
T. Z. Berardini, K. Bollman, H. Sun, and R. Scott Poethig (2001)
Science 291, 2405-2407
   Abstract »    Full Text »
Molecular Chaperone Interactions with Steroid Receptors: an Update.
J. Cheung and D. F. Smith (2000)
Mol. Endocrinol. 14, 939-946
   Full Text »
A Role for the Hsp40 Ydj1 in Repression of Basal Steroid Receptor Activity in Yeast.
J. L. Johnson and E. A. Craig (2000)
Mol. Cell. Biol. 20, 3027-3036
   Abstract »    Full Text »
Apoptosis, mitosis and cyclophilin-40 expression in regressing peroxisome proliferator-induced adenomas.
R. T. Miller, S. P. Anderson, J.C. Corton, and R. C. Cattley (2000)
Carcinogenesis 21, 647-652
   Abstract »    Full Text »    PDF »
The p23 molecular chaperones act at a late step in intracellular receptor action to differentially affect ligand efficacies.
B. C. Freeman, S. J. Felts, D. O. Toft, and K. R. Yamamoto (2000)
Genes & Dev. 14, 422-434
   Abstract »    Full Text »
The Identification of Wos2, a p23 Homologue That Interacts With Wee1 and Cdc2 in the Mitotic Control of Fission Yeasts.
M. J. Muñoz, E. R. Bejarano, R. R. Daga, and J. Jimenez (1999)
Genetics 153, 1561-1572
   Abstract »    Full Text »
Antifungal Activities of Antineoplastic Agents: Saccharomyces cerevisiae as a Model System To Study Drug Action.
M. E. Cardenas, M. C. Cruz, M. Del Poeta, N. Chung, J. R. Perfect, and J. Heitman (1999)
Clin. Microbiol. Rev. 12, 583-611
   Abstract »    Full Text »    PDF »
The Yeast Hsp110 Family Member, Sse1, Is an Hsp90 Cochaperone.
X.-D. Liu, K. A. Morano, and D. J. Thiele (1999)
J. Biol. Chem. 274, 26654-26660
   Abstract »    Full Text »    PDF »
Role for Hsp90-Associated Cochaperone p23 in Estrogen Receptor Signal Transduction.
R. Knoblauch and M. J. Garabedian (1999)
Mol. Cell. Biol. 19, 3748-3759
   Abstract »    Full Text »    PDF »
Identification of SSF1, CNS1, and HCH1 as multicopy suppressors of a Saccharomyces cerevisiae Hsp90 loss-of-function mutation.
D. F. Nathan, M. H. Vos, and S. Lindquist (1999)
PNAS 96, 1409-1414
   Abstract »    Full Text »    PDF »
Glucocorticoid Resistance in the Squirrel Monkey Is Associated with Overexpression of the Immunophilin FKBP51.
P. D. Reynolds, Y. Ruan, D. F. Smith, and J. G. Scammell (1999)
J. Clin. Endocrinol. Metab. 84, 663-669
   Abstract »    Full Text »
The Common Tetratricopeptide Repeat Acceptor Site for Steroid Receptor-associated Immunophilins and Hop Is Located in the Dimerization Domain of Hsp90.
A. Carrello, E. Ingley, R. F. Minchin, S. Tsai, and T. Ratajczak (1999)
J. Biol. Chem. 274, 2682-2689
   Abstract »    Full Text »    PDF »
Maturation of the tyrosine kinase c-src as a kinase and as a substrate depends on the molecular chaperone Hsp90.
Y. Xu, M. A. Singer, and S. Lindquist (1999)
PNAS 96, 109-114
   Abstract »    Full Text »    PDF »
A trans-Activation Domain in Yeast Heat Shock Transcription Factor Is Essential for Cell Cycle Progression during Stress.
K. A. Morano, N. Santoro, K. A. Koch, and D. J. Thiele (1999)
Mol. Cell. Biol. 19, 402-411
   Abstract »    Full Text »    PDF »
Characterization of the Ah Receptor-associated Protein, ARA9.
L. A. Carver, J. J. LaPres, S. Jain, E. E. Dunham, and C. A. Bradfield (1998)
J. Biol. Chem. 273, 33580-33587
   Abstract »    Full Text »    PDF »
CNS1 Encodes an Essential p60/Sti1 Homolog in Saccharomyces cerevisiae That Suppresses Cyclophilin 40 Mutations and Interacts with Hsp90.
K. J. Dolinski, M. E. Cardenas, and J. Heitman (1998)
Mol. Cell. Biol. 18, 7344-7352
   Abstract »    Full Text »
Cns1 Is an Essential Protein Associated with the Hsp90 Chaperone Complex in Saccharomyces cerevisiae That Can Restore Cyclophilin 40-Dependent Functions in cpr7Delta Cells.
J. A. Marsh, H. M. Kalton, and R. F. Gaber (1998)
Mol. Cell. Biol. 18, 7353-7359
   Abstract »    Full Text »
Requirement for Hsp90 and a CyP-40-type Cyclophilin in Negative Regulation of the Heat Shock Response.
A. A. Duina, H. M. Kalton, and R. F. Gaber (1998)
J. Biol. Chem. 273, 18974-18978
   Abstract »    Full Text »    PDF »
SBA1 Encodes a Yeast Hsp90 Cochaperone That Is Homologous to Vertebrate p23 Proteins.
Y. Fang, A. E. Fliss, J. Rao, and A. J. Caplan (1998)
Mol. Cell. Biol. 18, 3727-3734
   Abstract »    Full Text »
Agrobacterium VirD2 protein interacts with plant host cyclophilins.
W. Deng, L. Chen, D. W. Wood, T. Metcalfe, X. Liang, M. P. Gordon, L. Comai, and E. W. Nester (1998)
PNAS 95, 7040-7045
   Abstract »    Full Text »    PDF »
Genetic and Biochemical Analysis of p23 and Ansamycin Antibiotics in the Function of Hsp90-Dependent Signaling Proteins.
S. P. Bohen (1998)
Mol. Cell. Biol. 18, 3330-3339
   Abstract »    Full Text »
Involvement of Molecular Chaperonins in Nucleotide Excision Repair. DnaK LEADS TO INCREASED THERMAL STABILITY OF UvrA, CATALYTIC UvrB LOADING, ENHANCED REPAIR, AND INCREASED UV RESISTANCE.
Y. Zou, D. J. Crowley, and B. Van Houten (1998)
J. Biol. Chem. 273, 12887-12892
   Abstract »    Full Text »    PDF »
The Peptidyl-prolyl Isomerase Domain of the CyP-40 Cyclophilin Homolog Cpr7 Is Not Required to Support Growth or Glucocorticoid Receptor Activity in Saccharomyces cerevisiae.
A. A. Duina, J. A. Marsh, R. B. Kurtz, H.-C. J. Chang, S. Lindquist, and R. F. Gaber (1998)
J. Biol. Chem. 273, 10819-10822
   Abstract »    Full Text »    PDF »
Analysis of FKBP51/FKBP52 Chimeras and Mutants for Hsp90 Binding and Association with Progesterone Receptor Complexes.
R. L. Barent, S. C. Nair, D. C. Carr, Y. Ruan, R. A. Rimerman, J. Fulton, Y. Zhang, and D. F. Smith (1998)
Mol. Endocrinol. 12, 342-354
   Abstract »    Full Text »
Phosphorylation of the immunosuppressant FK506-binding protein FKBP52 by casein kinase II: Regulation of HSP90-binding activity of FKBP52.
Y. Miyata, B. Chambraud, C. Radanyi, J. Leclerc, M.-C. Lebeau, J.-M. Renoir, R. Shirai, M.-G. Catelli, I. Yahara, and E.-E. Baulieu (1997)
PNAS 94, 14500-14505
   Abstract »    Full Text »    PDF »
hsp110 Protects Heat-denatured Proteins and Confers Cellular Thermoresistance.
H. J. Oh, X. Chen, and J. R. Subjeck (1997)
J. Biol. Chem. 272, 31636-31640
   Abstract »    Full Text »    PDF »
In vivo functions of the Saccharomyces cerevisiae Hsp90 chaperone.
D. F. Nathan, M. H. Vos, and S. Lindquist (1997)
PNAS 94, 12949-12956
   Abstract »    Full Text »    PDF »
All cyclophilins and FK506 binding proteins are, individually and collectively, dispensable for viability in cerevisiae.
K. Dolinski, S. Muir, M. Cardenas, and J. Heitman (1997)
PNAS 94, 13093-13098
   Abstract »    Full Text »    PDF »
Cdc37 is a molecular chaperone with specific functions in signal transduction..
Y Kimura, S L Rutherford, Y Miyata, I Yahara, B C Freeman, L Yue, R I Morimoto, and S Lindquist (1997)
Genes & Dev. 11, 1775-1785
   Abstract »    PDF »
Protein Phosphatase 5 Is a Major Component of Glucocorticoid Receptor·hsp90 Complexes with Properties of an FK506-binding Immunophilin.
A. M. Silverstein, M. D. Galigniana, M.-S. Chen, J. K. Owens-Grillo, M. Chinkers, and W. B. Pratt (1997)
J. Biol. Chem. 272, 16224-16230
   Abstract »    Full Text »    PDF »
Ligand Interactions in the Adenosine Nucleotide-binding Domain of the Hsp90 Chaperone, GRP94. I. EVIDENCE FOR ALLOSTERIC REGULATION OF LIGAND BINDING.
M. F. N. Rosser and C. V. Nicchitta (2000)
J. Biol. Chem. 275, 22798-22805
   Abstract »    Full Text »    PDF »
Cpr6 and Cpr7, Two Closely Related Hsp90-associated Immunophilins from Saccharomyces cerevisiae, Differ in Their Functional Properties.
C. Mayr, K. Richter, H. Lilie, and J. Buchner (2000)
J. Biol. Chem. 275, 34140-34146
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)