|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 48, 45160-45167, November 30, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Induced expression of heat shock proteins
(Hsps) plays a central role in promoting cellular survival after
environmental and physiological stress. We have previously shown that
scrapie-infected mouse neuroblastoma (ScN2a) cells fail to induce the
expression of Hsp72 and Hsp28 after various stress conditions. Here we
present evidence that this impaired stress response is due to an
altered regulation of HSF1 activity. Upon stress in ScN2a cells, HSF1 was converted into hyperphosphorylated trimers but failed to acquire transactivation competence. A kinetic analysis of HSF1 activation revealed that in ScN2a cells trimer formation after stress was efficient, but disassembly of trimers proceeded much faster than in the
uninfected cell line. Geldanamycin, a Hsp90-binding drug, significantly
delayed disassembly of HSF1 trimers after a heat shock and restored
stress-induced expression of Hsp72 in ScN2a cells. Heat-induced Hsp72
expression required geldanamycin to be present; following removal of
the drug ScN2a cells again lost their ability to mount a stress
response. Thus, our studies show that a defective stress response can
be pharmacologically restored and suggest that the HSF1 deactivation
pathway may play an important role in the regulation of Hsp expression.
Geldanamycin Restores a Defective Heat Shock Response
in Vivo*
,,
Department of Cellular Biochemistry,
Max-Planck-Institut für Biochemie and the
§ Max-Planck-Institut für Neurobiologie, D-82152
Martinsried, Germany and the ¶ Department of Biochemistry and
Molecular Biology, University of Miami School of Medicine,
Miami, Florida 33101
*
This work was supported by Grant TA 167/2 from the Deutsche
Forschungsgemeinschaft.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of
Cellular Biochemistry, Max-Planck-Institut für Biochemie, D-82152
Martinsried, Germany. E-mail: tatzelt@biochem.mpg.de.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. K. McCollum, K. B. Lukasiewicz, C. J. TenEyck, W. L. Lingle, D. O. Toft, and C. Erlichman Cisplatin abrogates the geldanamycin-induced heat shock response Mol. Cancer Ther., October 1, 2008; 7(10): 3256 - 3264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. McCollum, C. J. TenEyck, B. Stensgard, B. W. Morlan, K. V. Ballman, R. B. Jenkins, D. O. Toft, and C. Erlichman P-Glycoprotein-Mediated Resistance to Hsp90-Directed Therapy Is Eclipsed by the Heat Shock Response Cancer Res., September 15, 2008; 68(18): 7419 - 7427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Steele, G. Hutter, W. S. Jackson, F. L. Heppner, A. W. Borkowski, O. D. King, G. J. Raymond, A. Aguzzi, and S. Lindquist Heat shock factor 1 regulates lifespan as distinct from disease onset in prion disease PNAS, September 9, 2008; 105(36): 13626 - 13631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zoubeidi, A. Zardan, E. Beraldi, L. Fazli, R. Sowery, P. Rennie, C. Nelson, and M. Gleave Cooperative Interactions between Androgen Receptor (AR) and Heat-Shock Protein 27 Facilitate AR Transcriptional Activity Cancer Res., November 1, 2007; 67(21): 10455 - 10465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Poulaki, E. Iliaki, N. Mitsiades, C. S. Mitsiades, Y. N. Paulus, D. V. Bula, E. S. Gragoudas, and J. W. Miller Inhibition of Hsp90 attenuates inflammation in endotoxin-induced uveitis FASEB J, July 1, 2007; 21(9): 2113 - 2123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. H. Henn, L. Bouman, J. S. Schlehe, A. Schlierf, J. E. Schramm, E. Wegener, K. Nakaso, C. Culmsee, B. Berninger, D. Krappmann, et al. Parkin Mediates Neuroprotection through Activation of I{kappa}B Kinase/Nuclear Factor-{kappa}B Signaling J. Neurosci., February 21, 2007; 27(8): 1868 - 1878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. McCollum, C. J. TenEyck, B. M. Sauer, D. O. Toft, and C. Erlichman Up-regulation of Heat Shock Protein 27 Induces Resistance to 17-Allylamino-Demethoxygeldanamycin through a Glutathione-Mediated Mechanism. Cancer Res., November 15, 2006; 66(22): 10967 - 10975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-Y. Shen, J.-C. He, Y. Wang, Q.-Y. Huang, and J.-F. Chen Geldanamycin Induces Heat Shock Protein 70 and Protects against MPTP-induced Dopaminergic Neurotoxicity in Mice J. Biol. Chem., December 2, 2005; 280(48): 39962 - 39969. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Bertsch, K. F. Winklhofer, T. Hirschberger, J. Bieschke, P. Weber, F. U. Hartl, P. Tavan, J. Tatzelt, H. A. Kretzschmar, and A. Giese Systematic Identification of Antiprion Drugs by High-Throughput Screening Based on Scanning for Intensely Fluorescent Targets J. Virol., June 15, 2005; 79(12): 7785 - 7791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kiachopoulos, A. Bracher, K. F. Winklhofer, and J. Tatzelt Pathogenic Mutations Located in the Hydrophobic Core of the Prion Protein Interfere with Folding and Attachment of the Glycosylphosphatidylinositol Anchor J. Biol. Chem., March 11, 2005; 280(10): 9320 - 9329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Uelhoff, J. Tatzelt, A. Aguzzi, K. F. Winklhofer, and C. Haass A Pathogenic PrP Mutation and Doppel Interfere with Polarized Sorting of the Prion Protein J. Biol. Chem., February 18, 2005; 280(7): 5137 - 5140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. Mimnaugh, W. Xu, M. Vos, X. Yuan, J. S. Isaacs, K. S. Bisht, D. Gius, and L. Neckers Simultaneous inhibition of hsp 90 and the proteasome promotes protein ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and enhances antitumor activity Mol. Cancer Ther., May 1, 2004; 3(5): 551 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. F. Winklhofer, I. H. Henn, P. C. Kay-Jackson, U. Heller, and J. Tatzelt Inactivation of Parkin by Oxidative Stress and C-terminal Truncations: A PROTECTIVE ROLE OF MOLECULAR CHAPERONES J. Biol. Chem., November 21, 2003; 278(47): 47199 - 47208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Rosenhagen, C. Soti, U. Schmidt, G. M. Wochnik, F. U. Hartl, F. Holsboer, J. C. Young, and T. Rein The Heat Shock Protein 90-Targeting Drug Cisplatin Selectively Inhibits Steroid Receptor Activation Mol. Endocrinol., October 1, 2003; 17(10): 1991 - 2001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Heller, K. F. Winklhofer, J. Heske, A. Reintjes, and J. Tatzelt Post-translational Import of the Prion Protein into the Endoplasmic Reticulum Interferes with Cell Viability: A CRITICAL ROLE FOR THE PUTATIVE TRANSMEMBRANE DOMAIN J. Biol. Chem., September 19, 2003; 278(38): 36139 - 36147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Batulan, G. A. Shinder, S. Minotti, B. P. He, M. M. Doroudchi, J. Nalbantoglu, M. J. Strong, and H. D. Durham High Threshold for Induction of the Stress Response in Motor Neurons Is Associated with Failure to Activate HSF1 J. Neurosci., July 2, 2003; 23(13): 5789 - 5798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. F. Winklhofer, J. Heske, U. Heller, A. Reintjes, W. Muranyi, I. Moarefi, and J. Tatzelt Determinants of the in Vivo Folding of the Prion Protein. A BIPARTITE FUNCTION OF HELIX 1 IN FOLDING AND AGGREGATION J. Biol. Chem., April 18, 2003; 278(17): 14961 - 14970. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. B. Graefe, M. Wiesgigl, I. Gaworski, A. Macdonald, and J. Clos Inhibition of HSP90 in Trypanosoma cruzi Induces a Stress Response but No Stage Differentiation Eukaryot. Cell, December 1, 2002; 1(6): 936 - 943. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |