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.


Logo for

Mol. Biol. Cell 11 (4): 1169-1181

Copyright © 2000 by The American Society for Cell Biology.

Vol. 11, Issue 4, 1169-1181, April 2000

Multistep Phosphorelay Proteins Transmit Oxidative Stress Signals to the Fission Yeast Stress-activated Protein Kinase

Aaron Ngocky Nguyen, Albert Lee, Warren Place, and Kazuhiro Shiozaki*

Section of Microbiology, University of California, Davis, California 95616

In response to oxidative stress, eukaryotic cells induce transcription of genes required for detoxification of oxidants. Here we present evidence that oxidative stress stimuli are transmitted by a multistep phosphorelay system to the Spc1/Sty1 stress-activated protein kinase in the fission yeast Schizosaccharomyces pombe. The fission yeast mpr1+ gene encodes a novel protein with a histidine-containing phosphotransfer domain homologous to the budding yeast Ypd1. Spc1 activation upon oxidative stress is severely impaired in the Delta mpr1 mutant as well as in the mpr1HQ strain, in which the putative phosphorylation site Mpr1-His221 is substituted with glutamine. In response to oxidative stress, Mpr1 binds to the Mcs4 response regulator that functions upstream of the Spc1 cascade, suggesting that Mcs4 is a cognate response regulator for Mpr1. Unexpectedly, when exposed to hydrogen peroxide, Delta mpr1 cells can induce the catalase gene ctt1+, one of the transcriptional targets of the Spc1 pathway, and survive oxidative stress in the absence of significant Spc1 activation. We have found that Pap1, a bZIP transcription factor homologous to human c-Jun, can mediate induction of ctt1+ expression upon oxidative stress independently of the Spc1 stress-activated protein kinase. These studies show that oxidative stress stimuli are transmitted by multiple pathways to induce specific gene expression.

* Corresponding author. E-mail address: kshiozaki{at}

Molecular Biology of the Cell
Vol. 11, 1169-1181, April 2000
Copyright © 2000 by The American Society for Cell Biology

Histidine Phosphotransfer Proteins in Fungal Two-Component Signal Transduction Pathways.
J. S. Fassler and A. H. West (2013)
Eukaryot. Cell 12, 1052-1060
   Abstract »    Full Text »    PDF »
Response regulator-mediated MAPKKK heteromer promotes stress signaling to the Spc1 MAPK in fission yeast.
S. Morigasaki, A. Ikner, H. Tatebe, and K. Shiozaki (2013)
Mol. Biol. Cell 24, 1083-1092
   Abstract »    Full Text »    PDF »
The Neurospora crassa DCC-1 Protein, a Putative Histidine Kinase, Is Required for Normal Sexual and Asexual Development and Carotenogenesis.
C. Barba-Ostria, F. Lledias, and D. Georgellis (2011)
Eukaryot. Cell 10, 1733-1739
   Abstract »    Full Text »    PDF »
Multiple Roles of Ypd1 Phosphotransfer Protein in Viability, Stress Response, and Virulence Factor Regulation in Cryptococcus neoformans.
J.-W. Lee, Y.-J. Ko, S.-Y. Kim, and Y.-S. Bahn (2011)
Eukaryot. Cell 10, 998-1002
   Abstract »    Full Text »    PDF »
A novel family of dehydrin-like proteins is involved in stress response in the human fungal pathogen Aspergillus fumigatus.
J. W. S. Hoi, C. Lamarre, R. Beau, I. Meneau, A. Berepiki, A. Barre, E. Mellado, N. D. Read, and J.-P. Latge (2011)
Mol. Biol. Cell 22, 1896-1906
   Abstract »    Full Text »    PDF »
MAP Kinase Kinase Kinase (MAPKKK)-dependent and -independent Activation of Sty1 Stress MAPK in Fission Yeast.
X. Zhou, Y. Ma, R. Sugiura, D. Kobayashi, M. Suzuki, L. Deng, and T. Kuno (2010)
J. Biol. Chem. 285, 32818-32823
   Abstract »    Full Text »    PDF »
Hydrogen Peroxide-sensitive Cysteines in the Sty1 MAPK Regulate the Transcriptional Response to Oxidative Stress.
A. M. Day and E. A. Veal (2010)
J. Biol. Chem. 285, 7505-7516
   Abstract »    Full Text »    PDF »
Master and Commander in Fungal Pathogens: the Two-Component System and the HOG Signaling Pathway.
Y.-S. Bahn (2008)
Eukaryot. Cell 7, 2017-2036
   Full Text »    PDF »
Transcription Factors Pcr1 and Atf1 Have Distinct Roles in Stress- and Sty1-Dependent Gene Regulation.
M. Sanso, M. Gogol, J. Ayte, C. Seidel, and E. Hidalgo (2008)
Eukaryot. Cell 7, 826-835
   Abstract »    Full Text »    PDF »
Multiple Pathways Differentially Regulate Global Oxidative Stress Responses in Fission Yeast.
D. Chen, C. R. M. Wilkinson, S. Watt, C. J. Penkett, W. M. Toone, N. Jones, and J. Bahler (2008)
Mol. Biol. Cell 19, 308-317
   Abstract »    Full Text »    PDF »
Response Regulators SrrA and SskA Are Central Components of a Phosphorelay System Involved in Stress Signal Transduction and Asexual Sporulation in Aspergillus nidulans.
I. Vargas-Perez, O. Sanchez, L. Kawasaki, D. Georgellis, and J. Aguirre (2007)
Eukaryot. Cell 6, 1570-1583
   Abstract »    Full Text »    PDF »
Regulation of Schizosaccharomyces pombe Atf1 Protein Levels by Sty1-mediated Phosphorylation and Heterodimerization with Pcr1.
C. L. Lawrence, H. Maekawa, J. L. Worthington, W. Reiter, C. R. M. Wilkinson, and N. Jones (2007)
J. Biol. Chem. 282, 5160-5170
   Abstract »    Full Text »    PDF »
Sclerotial metamorphosis in filamentous fungi is induced by oxidative stress.
C. D. Georgiou, N. Patsoukis, I. Papapostolou, and G. Zervoudakis (2006)
Integr. Comp. Biol. 46, 691-712
   Abstract »    Full Text »    PDF »
Repression of ergosterol level during oxidative stress by fission yeast F-box protein Pof14 independently of SCF.
L. Tafforeau, S. Le Blastier, S. Bamps, M. Dewez, J. Vandenhaute, and D. Hermand (2006)
EMBO J. 25, 4547-4556
   Abstract »    Full Text »    PDF »
Fungal responses to reactive oxygen species.
J. Aguirre, W. Hansberg, and R. Navarro (2006)
Med Mycol 44, S101-S107
   Abstract »    Full Text »    PDF »
Methylglyoxal as a Signal Initiator for Activation of the Stress-activated Protein Kinase Cascade in the Fission Yeast Schizosaccharomyces pombe.
Y. Takatsume, S. Izawa, and Y. Inoue (2006)
J. Biol. Chem. 281, 9086-9092
   Abstract »    Full Text »    PDF »
Cip1 and Cip2 Are Novel RNA-Recognition-Motif Proteins That Counteract Csx1 Function during Oxidative Stress.
V. Martin, M. A. Rodriguez-Gabriel, W. H. McDonald, S. Watt, J. R. Yates III, J. Bahler, and P. Russell (2006)
Mol. Biol. Cell 17, 1176-1183
   Abstract »    Full Text »    PDF »
Stress-Activated Protein Kinase Pathway Functions To Support Protein Synthesis and Translational Adaptation in Response to Environmental Stress in Fission Yeast.
I. Dunand-Sauthier, C. A. Walker, J. Narasimhan, A. K. Pearce, R. C. Wek, and T. C. Humphrey (2005)
Eukaryot. Cell 4, 1785-1793
   Abstract »    Full Text »    PDF »
Distinct Signaling Pathways Respond to Arsenite and Reactive Oxygen Species in Schizosaccharomyces pombe.
M. A. Rodriguez-Gabriel and P. Russell (2005)
Eukaryot. Cell 4, 1396-1402
   Abstract »    Full Text »    PDF »
Atf1-Pcr1-M26 Complex Links Stress-activated MAPK and cAMP-dependent Protein Kinase Pathways via Chromatin Remodeling of cgs2+.
M. K. Davidson, H. K. Shandilya, K. Hirota, K. Ohta, and W. P. Wahls (2004)
J. Biol. Chem. 279, 50857-50863
   Abstract »    Full Text »    PDF »
Differential Activation of eIF2 Kinases in Response to Cellular Stresses in Schizosaccharomyces pombe.
K. Zhan, J. Narasimhan, and R. C. Wek (2004)
Genetics 168, 1867-1875
   Abstract »    Full Text »    PDF »
A Cooperative Role for Atf1 and Pap1 in the Detoxification of the Oxidative Stress Induced by Glucose Deprivation in Schizosaccharomyces pombe.
M. Madrid, T. Soto, A. Franco, V. Paredes, J. Vicente, E. Hidalgo, M. Gacto, and J. Cansado (2004)
J. Biol. Chem. 279, 41594-41602
   Abstract »    Full Text »    PDF »
Global Gene Expression Responses of Fission Yeast to Ionizing Radiation.
A. Watson, J. Mata, J. Bahler, A. Carr, and T. Humphrey (2004)
Mol. Biol. Cell 15, 851-860
   Abstract »    Full Text »    PDF »
RNA-binding protein Csx1 mediates global control of gene expression in response to oxidative stress.
M. A. Rodriguez-Gabriel, G. Burns, W. H. McDonald, V. Martin, J. R. Yates III, J. Bahler, and P. Russell (2003)
EMBO J. 22, 6256-6266
   Abstract »    Full Text »    PDF »
Schizosaccharomyces pombe Cells Lacking the Ran-binding Protein Hba1 Show a Multidrug Resistance Phenotype Due to Constitutive Nuclear Accumulation of Pap1.
E. A. Castillo, A. P. Vivancos, N. Jones, J. Ayte, and E. Hidalgo (2003)
J. Biol. Chem. 278, 40565-40572
   Abstract »    Full Text »    PDF »
Identification of Cdc37 as a Novel Regulator of the Stress-Responsive Mitogen-Activated Protein Kinase.
H. Tatebe and K. Shiozaki (2003)
Mol. Cell. Biol. 23, 5132-5142
   Abstract »    Full Text »    PDF »
Regulation of the Transcriptional Response to Oxidative Stress in Fungi: Similarities and Differences.
W. S. Moye-Rowley (2003)
Eukaryot. Cell 2, 381-389
   Full Text »    PDF »
Global Transcriptional Responses of Fission Yeast to Environmental Stress.
D. Chen, W. M. Toone, J. Mata, R. Lyne, G. Burns, K. Kivinen, A. Brazma, N. Jones, and J. Bahler (2003)
Mol. Biol. Cell 14, 214-229
   Abstract »    Full Text »
Phosphorylation of Eukaryotic Initiation Factor 2 by Heme-Regulated Inhibitor Kinase-Related Protein Kinases in Schizosaccharomyces pombe Is Important for Resistance to Environmental Stresses.
K. Zhan, K. M. Vattem, B. N. Bauer, T. E. Dever, J.-J. Chen, and R. C. Wek (2002)
Mol. Cell. Biol. 22, 7134-7146
   Abstract »    Full Text »    PDF »
Role of Fission Yeast Tup1-like Repressors and Prr1 Transcription Factor in Response to Salt Stress.
A. Greenall, A. P. Hadcroft, P. Malakasi, N. Jones, B. A. Morgan, C. S. Hoffman, and S. K. Whitehall (2002)
Mol. Biol. Cell 13, 2977-2989
   Abstract »    Full Text »    PDF »
The Srk1 Protein Kinase Is a Target for the Sty1 Stress-activated MAPK in Fission Yeast.
D. A. Smith, W. M. Toone, D. Chen, J. Bahler, N. Jones, B. A. Morgan, and J. Quinn (2002)
J. Biol. Chem. 277, 33411-33421
   Abstract »    Full Text »    PDF »
Osmotic Stress Signaling and Osmoadaptation in Yeasts.
S. Hohmann (2002)
Microbiol. Mol. Biol. Rev. 66, 300-372
   Abstract »    Full Text »    PDF »
The Serine/Threonine Kinase Cmk2 Is Required for Oxidative Stress Response in Fission Yeast.
M. Sanchez-Piris, F. Posas, V. Alemany, I. Winge, E. Hidalgo, O. Bachs, and R. Aligue (2002)
J. Biol. Chem. 277, 17722-17727
   Abstract »    Full Text »    PDF »
Counteracting Regulation of Chromatin Remodeling at a Fission Yeast cAMP Responsive Element-Related Recombination Hotspot by Stress-Activated Protein Kinase, cAMP-Dependent Kinase and Meiosis Regulators.
K.-i. Mizuno, T. Hasemi, T. Ubukata, T. Yamada, E. Lehmann, J. Kohli, Y. Watanabe, Y. Iino, M. Yamamoto, M. E. Fox, et al. (2001)
Genetics 159, 1467-1478
   Abstract »    Full Text »    PDF »
Fungal Histidine Kinases.
J. L. Santos and K. Shiozaki (2001)
Sci. STKE 2001, re1
   Abstract »    Full Text »    PDF »
Peroxide Sensors for the Fission Yeast Stress-activated Mitogen-activated Protein Kinase Pathway.
V. Buck, J. Quinn, T. S. Pino, H. Martin, J. Saldanha, K. Makino, B. A. Morgan, and J. B.A. Millar (2001)
Mol. Biol. Cell 12, 407-419
   Abstract »    Full Text »
Eukaryotic signal transduction via histidine-aspartate phosphorelay.
P. Thomason and R. Kay (2000)
J. Cell Sci. 113, 3141-3150
   Abstract »    PDF »
Spy1, a Histidine-Containing Phosphotransfer Signaling Protein, Regulates the Fission Yeast Cell Cycle through the Mcs4 Response Regulator.
K. Aoyama, Y. Mitsubayashi, H. Aiba, and T. Mizuno (2000)
J. Bacteriol. 182, 4868-4874
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

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