|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 9, 7430-7437, March 1, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Biochemistry, New York University School of
Medicine, New York, New York 10016
Hsp90 plays critical roles in the proper
functioning of a wide array of eukaryotic signal transducers such as
steroid receptors and tyrosine kinases. Hap1 is a naturally occurring
substrate of Hsp90 in Saccharomyces cerevisiae. Hap1
transcriptional activity is precisely and stringently controlled by
heme. Previous biochemical studies suggest that in the absence of heme,
Hap1 is bound to Hsp90 and other proteins, forming a higher order
complex termed HMC (high molecular weight complex), and is repressed.
Heme promotes the disruption of the HMC and activates Hap1, permitting
Hap1 to bind to DNA with high affinity and to stimulate transcription. By lowering the expression levels of wild-type Hsp90, using a highly
specific Hsp90 inhibitor, and by examining the effects of various Hsp90
mutants on Hap1, we show that Hsp90 is critical for Hap1 activation by
heme. Furthermore, we show that many Hsp90 mutants exert differential
effects on Hap1 and steroid receptors. Notably, mutant G313N weakens
Hsp90 steroid receptor interaction but strongly enhances Hsp90-Hap1
interaction and increases Hap1 resistance to protease digestion.
Additionally, we found that a heme-independent Hap1 mutant still
depends on Hsp90 for high activity. These experiments together suggest
that Hsp90 promotes Hap1 activation by inducing or maintaining Hap1 in
a transcriptionally active conformation.
The Molecular Chaperone Hsp90 Mediates Heme Activation of the
Yeast Transcriptional Activator Hap1*
*
This work was supported by National Institutes of Health
Grant GM53453 (to L. Z.).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.
Monique Weill-Caulier Scholar. To whom correspondence
should be addressed. Tel.: 212-263-8506; Fax: 212-263-8166; E-mail: li.zhang@med.nyu.edu.
Copyright © 2002 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:
|
|
 |
|
  M. Floer, G. O. Bryant, and M. Ptashne HSP90/70 chaperones are required for rapid nucleosome removal upon induction of the GAL genes of yeast PNAS, February 26, 2008; 105(8): 2975 - 2980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Hickman and F. Winston Heme Levels Switch the Function of Hap1 of Saccharomyces cerevisiae between Transcriptional Activator and Transcriptional Repressor Mol. Cell. Biol., November 1, 2007; 27(21): 7414 - 7424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Shahi, K. Gulshan, and W. S. Moye-Rowley Negative Transcriptional Regulation of Multidrug Resistance Gene Expression by an Hsp70 Protein J. Biol. Chem., September 14, 2007; 282(37): 26822 - 26831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Wright, S. W. Fewell, M. L. Sullivan, J. M. Pipas, S. C. Watkins, and J. L. Brodsky The Hsp40 Molecular Chaperone Ydj1p, Along With the Protein Kinase C Pathway, Affects Cell-Wall Integrity in the Yeast Saccharomyces cerevisiae Genetics, April 1, 2007; 175(4): 1649 - 1664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bernreiter, A. Ramon, J. Fernandez-Martinez, H. Berger, L. Araujo-Bazan, E. A. Espeso, R. Pachlinger, A. Gallmetzer, I. Anderl, C. Scazzocchio, et al. Nuclear Export of the Transcription Factor NirA Is a Regulatory Checkpoint for Nitrate Induction in Aspergillus nidulans Mol. Cell. Biol., February 1, 2007; 27(3): 791 - 802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Som, R. N. Mitsch, J. L. Urbanowski, and R. J. Rolfes DNA-Bound Bas1 Recruits Pho2 To Activate ADE Genes in Saccharomyces cerevisiae Eukaryot. Cell, October 1, 2005; 4(10): 1725 - 1735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hon, H. C. Lee, Z. Hu, V. R. Iyer, and L. Zhang The Heme Activator Protein Hap1 Represses Transcription by a Heme-Independent Mechanism in Saccharomyces cerevisiae Genetics, March 1, 2005; 169(3): 1343 - 1352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lan, H. C. Lee, S. Tang, and L. Zhang A Novel Mode of Chaperone Action: HEME ACTIVATION OF Hap1 BY ENHANCED ASSOCIATION OF Hsp90 WITH THE REPRESSED Hsp70-Hap1 COMPLEX J. Biol. Chem., June 25, 2004; 279(26): 27607 - 27612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bali, B. Zhang, K. A. Morano, and C. A. Michels The Hsp90 Molecular Chaperone Complex Regulates Maltose Induction and Stability of the Saccharomyces MAL Gene Transcription Activator Mal63p J. Biol. Chem., November 28, 2003; 278(48): 47441 - 47448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. D. T. G. Wagener, H.-D. Volk, D. Willis, N. G. Abraham, M. P. Soares, G. J. Adema, and C. G. Figdor Different Faces of the Heme-Heme Oxygenase System in Inflammation Pharmacol. Rev., September 1, 2003; 55(3): 551 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. C. Lee, T. Hon, C. Lan, and L. Zhang Structural Environment Dictates the Biological Significance of Heme-Responsive Motifs and the Role of Hsp90 in the Activation of the Heme Activator Protein Hap1 Mol. Cell. Biol., August 15, 2003; 23(16): 5857 - 5866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Osawa, E. R. Lowe, A. C. Everett, A. Y. Dunbar, and S. S. Billecke Proteolytic Degradation of Nitric Oxide Synthase: Effect of Inhibitors and Role of hsp90-Based Chaperones J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 493 - 497. [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 |