This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bohen, S. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bohen, S. P.

 Previous Article  |  Next Article 

Mol Cell Biol, June 1998, p. 3330-3339, Vol. 18, No. 6
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Genetic and Biochemical Analysis of p23 and Ansamycin Antibiotics in the Function of Hsp90-Dependent Signaling Proteins

Sean P. Bohen*

Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255

Received 17 October 1997/Returned for modification 15 December 1997/Accepted 6 March 1998

The ubiquitous molecular chaperone Hsp90 acts in concert with a cohort of associated proteins to facilitate the functional maturation of a number of cellular signaling proteins, such as steroid hormone receptors and oncogene tyrosine kinases. The Hsp90-associated protein p23 is required for the assembly of functional steroid aporeceptor complexes in cell lysates, and Hsp90-binding ansamycin antibiotics disrupt the activity of Hsp90-dependent signaling proteins in cultured mammalian cells and prevent the association of p23 with Hsp90-receptor heterocomplexes; these observations have led to the hypotheses that p23 is required for the maturation of Hsp90 target proteins and that ansamycin antibiotics abrogate the activity of such proteins by disrupting the interaction of p23 with Hsp90. In this study, I demonstrate that ansamycin antibiotics disrupt the function of Hsp90 target proteins expressed in yeast cells; prevent the assembly of Sba1, a yeast p23-like protein, into steroid receptor-Hsp90 complexes; and result in the assembly of receptor-Hsp90 complexes that are defective for ligand binding. To assess the role of p23 in Hsp90 target protein function, I show that the activity of Hsp90 target proteins is unaffected by deletion of SBA1. Interestingly, steroid receptor activity in cells lacking Sba1 displays increased sensitivity to ansamycin antibiotics, and this phenotype is rescued by the expression of human p23 in yeast cells. These findings indicate that Hsp90-dependent signaling proteins can achieve a functional conformation in vivo in the absence of p23. Furthermore, while the presence of p23 decreases the sensitivity of Hsp90-dependent processes to ansamycin treatment, ansamycin antibiotics disrupt signaling through some mechanism other than altering the Hsp90-p23 interaction.

* Present address: University of California-San Francisco, Department of Medicine, San Francisco, CA 94143. Phone: (415) 661-4775. Fax: (415) 476-6129. E-mail: bohens{at}itsa.ucsf.edu.

Mol Cell Biol, June 1998, p. 3330-3339, Vol. 18, No. 6
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Berry, N. B., Fan, M., Nephew, K. P. (2008). Estrogen Receptor-{alpha} Hinge-Region Lysines 302 and 303 Regulate Receptor Degradation by the Proteasome. Mol. Endocrinol. 22: 1535-1551 [Abstract] [Full Text]  
  • Forafonov, F., Toogun, O. A., Grad, I., Suslova, E., Freeman, B. C., Picard, D. (2008). p23/Sba1p Protects against Hsp90 Inhibitors Independently of Its Intrinsic Chaperone Activity. Mol. Cell. Biol. 28: 3446-3456 [Abstract] [Full Text]  
  • Weeks, S. A., Miller, D. J. (2008). The Heat Shock Protein 70 Cochaperone YDJ1 Is Required for Efficient Membrane-Specific Flock House Virus RNA Replication Complex Assembly and Function in Saccharomyces cerevisiae. J. Virol. 82: 2004-2012 [Abstract] [Full Text]  
  • Grad, I., McKee, T. A., Ludwig, S. M., Hoyle, G. W., Ruiz, P., Wurst, W., Floss, T., Miller, C. A. III, Picard, D. (2006). The Hsp90 Cochaperone p23 Is Essential for Perinatal Survival. Mol. Cell. Biol. 26: 8976-8983 [Abstract] [Full Text]  
  • Keppler, B. R., Grady, A. T., Jarstfer, M. B. (2006). The Biochemical Role of the Heat Shock Protein 90 Chaperone Complex in Establishing Human Telomerase Activity. J. Biol. Chem. 281: 19840-19848 [Abstract] [Full Text]  
  • Arlander, S. J. H., Felts, S. J., Wagner, J. M., Stensgard, B., Toft, D. O., Karnitz, L. M. (2006). Chaperoning Checkpoint Kinase 1 (Chk1), an Hsp90 Client, with Purified Chaperones. J. Biol. Chem. 281: 2989-2998 [Abstract] [Full Text]  
  • Youker, R. T., Walsh, P., Beilharz, T., Lithgow, T., Brodsky, J. L. (2004). Distinct Roles for the Hsp40 and Hsp90 Molecular Chaperones during Cystic Fibrosis Transmembrane Conductance Regulator Degradation in Yeast. Mol. Biol. Cell 15: 4787-4797 [Abstract] [Full Text]  
  • Hainzl, O., Wegele, H., Richter, K., Buchner, J. (2004). Cns1 Is an Activator of the Ssa1 ATPase Activity. J. Biol. Chem. 279: 23267-23273 [Abstract] [Full Text]  
  • Lee, P., Shabbir, A., Cardozo, C., Caplan, A. J. (2004). Sti1 and Cdc37 Can Stabilize Hsp90 in Chaperone Complexes with a Protein Kinase. Mol. Biol. Cell 15: 1785-1792 [Abstract] [Full Text]  
  • Morishima, Y., Kanelakis, K. C., Murphy, P. J. M., Lowe, E. R., Jenkins, G. J., Osawa, Y., Sunahara, R. K., Pratt, W. B. (2003). The Hsp90 Cochaperone p23 Is the Limiting Component of the Multiprotein Hsp90/Hsp70-based Chaperone System in Vivo Where It Acts to Stabilize the Client Protein{middle dot}Hsp90 Complex. J. Biol. Chem. 278: 48754-48763 [Abstract] [Full Text]  
  • Cox, M. B., Miller, C. A. III (2003). Pharmacological and Genetic Analysis of 90-kDa Heat Shock Isoprotein-Aryl Hydrocarbon Receptor Complexes. Mol. Pharmacol. 64: 1549-1556 [Abstract] [Full Text]  
  • Bali, M., Zhang, B., Morano, K. A., Michels, C. A. (2003). The Hsp90 Molecular Chaperone Complex Regulates Maltose Induction and Stability of the Saccharomyces MAL Gene Transcription Activator Mal63p. J. Biol. Chem. 278: 47441-47448 [Abstract] [Full Text]  
  • Oxelmark, E., Knoblauch, R., Arnal, S., Su, L. F., Schapira, M., Garabedian, M. J. (2003). Genetic Dissection of p23, an Hsp90 Cochaperone, Reveals a Distinct Surface Involved in Estrogen Receptor Signaling. J. Biol. Chem. 278: 36547-36555 [Abstract] [Full Text]  
  • Tesic, M., Marsh, J. A., Cullinan, S. B., Gaber, R. F. (2003). Functional Interactions between Hsp90 and the Co-chaperones Cns1 and Cpr7 in Saccharomyces cerevisiae. J. Biol. Chem. 278: 32692-32701 [Abstract] [Full Text]  
  • Lotz, G. P., Lin, H., Harst, A., Obermann, W. M. J. (2003). Aha1 Binds to the Middle Domain of Hsp90, Contributes to Client Protein Activation, and Stimulates the ATPase Activity of the Molecular Chaperone. J. Biol. Chem. 278: 17228-17235 [Abstract] [Full Text]  
  • Pratt, W. B., Toft, D. O. (2003). Regulation of Signaling Protein Function and Trafficking by the hsp90/hsp70-Based Chaperone Machinery. Exp. Biol. Med. 228: 111-133 [Abstract] [Full Text]  
  • Lee, P., Rao, J., Fliss, A., Yang, E., Garrett, S., Caplan, A. J. (2002). The Cdc37 protein kinase-binding domain is sufficient for protein kinase activity and cell viability. JCB 159: 1051-1059 [Abstract] [Full Text]  
  • Lee, H. C., Hon, T., Zhang, L. (2002). The Molecular Chaperone Hsp90 Mediates Heme Activation of the Yeast Transcriptional Activator Hap1. J. Biol. Chem. 277: 7430-7437 [Abstract] [Full Text]  
  • Hu, J., Toft, D., Anselmo, D., Wang, X. (2002). In Vitro Reconstitution of Functional Hepadnavirus Reverse Transcriptase with Cellular Chaperone Proteins. J. Virol. 76: 269-279 [Abstract] [Full Text]  
  • Abbas-Terki, T., Donze, O., Briand, P.-A., Picard, D. (2001). Hsp104 Interacts with Hsp90 Cochaperones in Respiring Yeast. Mol. Cell. Biol. 21: 7569-7575 [Abstract] [Full Text]  
  • Johnson, J. L., Craig, E. A. (2000). A Role for the Hsp40 Ydj1 in Repression of Basal Steroid Receptor Activity in Yeast. Mol. Cell. Biol. 20: 3027-3036 [Abstract] [Full Text]  
  • Morishima, Y., Kanelakis, K. C., Silverstein, A. M., Dittmar, K. D., Estrada, L., Pratt, W. B. (2000). The Hsp Organizer Protein Hop Enhances the Rate of but Is Not Essential for Glucocorticoid Receptor Folding by the Multiprotein Hsp90-based Chaperone System. J. Biol. Chem. 275: 6894-6900 [Abstract] [Full Text]  
  • Freeman, B. C., Felts, S. J., Toft, D. O., Yamamoto, K. R. (2000). The p23 molecular chaperones act at a late step in intracellular receptor action to differentially affect ligand efficacies. Genes Dev. 14: 422-434 [Abstract] [Full Text]  
  • Donze, O., Picard, D. (1999). Hsp90 Binds and Regulates the Ligand-Inducible alpha Subunit of Eukaryotic Translation Initiation Factor Kinase Gcn2. Mol. Cell. Biol. 19: 8422-8432 [Abstract] [Full Text]  
  • Panaretou, B., Sinclair, K., Prodromou, C., Johal, J., Pearl, L., Piper, P. W. (1999). The Hsp90 of Candida albicans can confer Hsp90 functions in Saccharomyces cerevisiae: a potential model for the processes that generate immunogenic fragments of this molecular chaperone in C. albicans infections. Microbiology 145: 3455-3463 [Abstract] [Full Text]  
  • Muñoz, M. J., Bejarano, E. R., Daga, R. R., Jimenez, J. (1999). The Identification of Wos2, a p23 Homologue That Interacts With Wee1 and Cdc2 in the Mitotic Control of Fission Yeasts. Genetics 153: 1561-1572 [Abstract] [Full Text]  
  • Cardenas, M. E., Cruz, M. C., Del Poeta, M., Chung, N., Perfect, J. R., Heitman, J. (1999). Antifungal Activities of Antineoplastic Agents: Saccharomyces cerevisiae as a Model System To Study Drug Action. Clin. Microbiol. Rev. 12: 583-611 [Abstract] [Full Text]  
  • Liu, X.-D., Morano, K. A., Thiele, D. J. (1999). The Yeast Hsp110 Family Member, Sse1, Is an Hsp90 Cochaperone. J. Biol. Chem. 274: 26654-26660 [Abstract] [Full Text]  
  • Knoblauch, R., Garabedian, M. J. (1999). Role for Hsp90-Associated Cochaperone p23 in Estrogen Receptor Signal Transduction. Mol. Cell. Biol. 19: 3748-3759 [Abstract] [Full Text]  
  • Kosano, H., Stensgard, B., Charlesworth, M. C., McMahon, N., Toft, D. (1998). The Assembly of Progesterone Receptor-hsp90 Complexes Using Purified Proteins. J. Biol. Chem. 273: 32973-32979 [Abstract] [Full Text]  
  • Dolinski, K. J., Cardenas, M. E., Heitman, J. (1998). CNS1 Encodes an Essential p60/Sti1 Homolog in Saccharomyces cerevisiae That Suppresses Cyclophilin 40 Mutations and Interacts with Hsp90. Mol. Cell. Biol. 18: 7344-7352 [Abstract] [Full Text]  
  • Obermann, W. M.J., Sondermann, H., Russo, A. A., Pavletich, N. P., Hartl, F. U. (1998). In Vivo Function of Hsp90 Is Dependent on ATP Binding and ATP Hydrolysis. JCB 143: 901-910 [Abstract] [Full Text]  
  • Weaver, A. J., Sullivan, W. P., Felts, S. J., Owen, B. A. L., Toft, D. O. (2000). Crystal Structure and Activity of Human p23, a Heat Shock Protein 90 Co-chaperone. J. Biol. Chem. 275: 23045-23052 [Abstract] [Full Text]  
  • Tanioka, T., Nakatani, Y., Semmyo, N., Murakami, M., Kudo, I. (2000). Molecular Identification of Cytosolic Prostaglandin E2 Synthase That Is Functionally Coupled with Cyclooxygenase-1 in Immediate Prostaglandin E2 Biosynthesis. J. Biol. Chem. 275: 32775-32782 [Abstract] [Full Text]  
  • Scholz, G. M., Cartledge, K., Hall, N. E. (2001). Identification and Characterization of Harc, a Novel Hsp90-associating Relative of Cdc37. J. Biol. Chem. 276: 30971-30979 [Abstract] [Full Text]  
  • Chadli, A., Bouhouche, I., Sullivan, W., Stensgard, B., McMahon, N., Catelli, M. G., Toft, D. O. (2000). Dimerization and N-terminal domain proximity underlie the function of the molecular chaperone heat shock protein 90. Proc. Natl. Acad. Sci. USA 97: 12524-12529 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»