Error message

No crossref credentials set for mcb

The Hsp70-Ydj1 Molecular Chaperone Represses the Activity of the Heme Activator Protein Hap1 in the Absence of Heme

Mol. Cell. Biol., 1 December 2001
Vol. 21, Issue 23, p. 7923-7932
DOI: 10.1128/MCB.21.23.7923-7932.2001

The Hsp70-Ydj1 Molecular Chaperone Represses the Activity of the Heme Activator Protein Hap1 in the Absence of Heme

  1. Thomas Hon1,
  2. Hee Chul Lee1,
  3. Angela Hach1,
  4. Jill L. Johnson2,
  5. Elizabeth A. Craig2,
  6. Hediye Erdjument-Bromage3,
  7. Paul Tempst3, and
  8. Li Zhang1,*
  1. Department of Biochemistry, NYU School of Medicine, New York, New York 100161;
  2. Department of Biomolecular Chemistry, University of Wisconsin, Madison, Wisconsin 537062; and
  3. Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 100213


In Saccharomyces cerevisiae, heme directly mediates the effects of oxygen on transcription through the heme activator protein Hap1. In the absence of heme, Hap1 is bound by at least four cellular proteins, including Hsp90 and Ydj1, forming a higher-order complex, termed HMC, and its activity is repressed. Here we purified the HMC and showed by mass spectrometry that two previously unidentified major components of the HMC are the Ssa-type Hsp70 molecular chaperone and Sro9 proteins. In vivo functional analysis, combined with biochemical analysis, strongly suggests that Ssa proteins are critical for Hap1 repression in the absence of heme. Ssa may repress the activities of both Hap1 DNA-binding and activation domains. The Ssa cochaperones Ydj1 and Sro9 appear to assist Ssa in Hap1 repression, and only Ydj1 residues 1 to 172 containing the J domain are required for Hap1 repression. Our results suggest that Ssa-Ydj1 and Sro9 act together to mediate Hap1 repression in the absence of heme and that molecular chaperones promote heme regulation of Hap1 by a mechanism distinct from the mechanism of steroid signaling.


    • Received 2 May 2001.
    • Accepted 27 August 2001.
  • * Corresponding author. Mailing address: Department of Biochemistry, NYU School of Medicine, 550 First Ave., New York, NY 10016. Phone: (212) 263-8506. Fax: (212) 263-8166. E-mail:li.zhang{at}


T. Hon, H. C. Lee, A. Hach, J. L. Johnson, E. A. Craig, H. Erdjument-Bromage, P. Tempst, and L. Zhang, The Hsp70-Ydj1 Molecular Chaperone Represses the Activity of the Heme Activator Protein Hap1 in the Absence of Heme. Mol. Cell. Biol. 21, 7923-7932 (2001).

Transcriptional Regulation in Saccharomyces cerevisiae: Transcription Factor Regulation and Function, Mechanisms of Initiation, and Roles of Activators and Coactivators
S. Hahn, and E. T. Young
Genetics 189, 705-736 (1 November 2011)

Farnesylation of Ydj1 Is Required for In Vivo Interaction with Hsp90 Client Proteins
G. A. Flom, M. Lemieszek, E. A. Fortunato, and J. L. Johnson
Mol. Biol. Cell 19, 5249-5258 (1 December 2008)

Metabolic control of transcription: paradigms and lessons from Saccharomyces cerevisiae
R. N. Campbell, M. K. Leverentz, L. A. Ryan, and R. J. Reece
Biochem. J. 414, 177-187 (1 September 2008)

Heme Levels Switch the Function of Hap1 of Saccharomyces cerevisiae between Transcriptional Activator and Transcriptional Repressor
M. J. Hickman, and F. Winston
Mol. Cell. Biol. 27, 7414-7424 (1 November 2007)

Negative Transcriptional Regulation of Multidrug Resistance Gene Expression by an Hsp70 Protein
P. Shahi, K. Gulshan, and W. S. Moye-Rowley
J Biol Chem 282, 26822-26831 (14 September 2007)

Total ancestry measure: quantifying the similarity in tree-like classification, with genomic applications
H. Yu, R. Jansen, G. Stolovitzky, and M. Gerstein
Bioinformatics 23, 2163-2173 (15 August 2007)

Nuclear Export of the Transcription Factor NirA Is a Regulatory Checkpoint for Nitrate Induction in Aspergillus nidulans
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.
Mol. Cell. Biol. 27, 791-802 (1 February 2007)

Characterization and prediction of protein-protein interactions within and between complexes
E. Sprinzak, Y. Altuvia, and H. Margalit
Proc. Natl. Acad. Sci. USA 103, 14718-14723 (3 October 2006)

The Heme Activator Protein Hap1 Represses Transcription by a Heme-Independent Mechanism in Saccharomyces cerevisiae
T. Hon, H. C. Lee, Z. Hu, V. R. Iyer, and L. Zhang
Genetics 169, 1343-1352 (1 March 2005)

C. Lan, H. C. Lee, S. Tang, and L. Zhang
J Biol Chem 279, 27607-27612 (25 June 2004)

T. Hon, A. Dodd, R. Dirmeier, N. Gorman, P. R. Sinclair, L. Zhang, and R. O. Poyton
J Biol Chem 278, 50771-50780 (12 December 2003)

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
J Biol Chem 278, 47441-47448 (28 November 2003)

Structural Environment Dictates the Biological Significance of Heme-Responsive Motifs and the Role of Hsp90 in the Activation of the Heme Activator Protein Hap1
H. C. Lee, T. Hon, C. Lan, and L. Zhang
Mol. Cell. Biol. 23, 5857-5866 (15 August 2003)

The Molecular Chaperone Hsp90 Mediates Heme Activation of the Yeast Transcriptional Activator Hap1
H. C. Lee, T. Hon, and L. Zhang
J Biol Chem 277, 7430-7437 (1 March 2002)

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882