Open AccessDistinct Signaling Pathways Respond to Arsenite and Reactive Oxygen Species in Schizosaccharomyces pombe
Author(s) -
M. Gabriel,
Paul Russell
Publication year - 2005
Publication title -
eukaryotic cell
Language(s) - English
Resource type - Journals
eISSN - 1535-9778
pISSN - 1535-9786
DOI - 10.1128/ec.4.8.1396-1402.2005
Subject(s) - schizosaccharomyces pombe , arsenite , reactive oxygen species , biology , sodium arsenite , oxidative stress , kinase , mapk/erk pathway , signal transduction , protein kinase a , p38 mitogen activated protein kinases , microbiology and biotechnology , biochemistry , transcription factor , arsenic , mutant , chemistry , organic chemistry , gene
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 atf1Delta pap1Delta 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.