Eukaryotic Cell
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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 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 Rodríguez-Gabriel, M. A.
Right arrow Articles by Russell, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rodríguez-Gabriel, M. A.
Right arrow Articles by Russell, P.
Eukaryotic Cell, August 2005, p. 1396-1402, Vol. 4, No. 8
1535-9778/05/$08.00+0     doi:10.1128/EC.4.8.1396-1402.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Distinct Signaling Pathways Respond to Arsenite and Reactive Oxygen Species in Schizosaccharomyces pombe

Miguel A. Rodríguez-Gabriel1,{dagger} and Paul Russell1,2*

Department of Molecular Biology,1 Department of Cell Biology, The Scripps Research Institute, La Jolla, California 920372

Received 10 May 2005/ Accepted 31 May 2005

Exposure to certain metal and metalloid species, such as arsenic, cadmium, chromium, and nickel, has been associated with an increased risk of cancer in humans. The biological effects of these metals are thought to result from induction of reactive oxygen species (ROS) and inhibition of DNA repair enzymes, although alterations in signal transduction pathways may also be involved in tumor development. To better understand metal toxicity and its connection to ROS, we have compared the effects of arsenite and hydrogen peroxide in wild-type and mutant strains of the fission yeast Schizosaccharomyces pombe. An atf1{Delta} pap1{Delta} strain, which is defective in two transcription factors that control stress responses, is extremely sensitive to hydrogen peroxide but not to arsenite. A strain that lacks the transcription factor Zip1 has the opposite relationship. Spc1 (Sty1) mitogen-activated protein kinase (MAPK), a homologue of mammalian p38 MAPK, and the upstream MAPK kinase (MAPKK) Wis1 are essential for survival of both arsenite and hydrogen peroxide. Inactivation of two MAPKK kinases, Win1 and Wis4, almost completely eliminates Spc1 activation by arsenite, yet these cells survive arsenite treatment. The two-component phosphorelay protein Mcs4, which acts upstream of Win1 and Wis4 and is required for Spc1 activation in response to oxidative stress, is not required for Spc1 activation in response to arsenite. We conclude that the toxic effects of arsenic are not strongly connected to oxidative stress and that although Spc1 is activated by arsenic exposure, the basal activity of Spc1 is largely sufficient for the survival of arsenic.

* Corresponding author. Mailing address: Department of Molecular Biology, MB3, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. Phone: (858) 784-8273. Fax: (858) 784-2265. E-mail: prussell{at}scripps.edu.

{dagger} Present address: Departamento de Microbiologia II, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.

Eukaryotic Cell, August 2005, p. 1396-1402, Vol. 4, No. 8
1535-9778/05/$08.00+0     doi:10.1128/EC.4.8.1396-1402.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Appl. Environ. Microbiol. Infect. Immun. J. Bacteriol.
Mol. Cell Biol. Microbiol. Mol. Biol. Rev. ALL ASM JOURNALS
Copyright © 2005 by the American Society for Microbiology.