Open AccessCentaurin‐like protein Cnt5 contributes to arsenic and cadmium resistance in fission yeast
Author(s) -
Vashisht Ajay Amar,
Kennedy Patrick Joseph,
Russell Paul
Publication year - 2009
Publication title -
fems yeast research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.991
H-Index - 92
eISSN - 1567-1364
pISSN - 1567-1356
DOI - 10.1111/j.1567-1364.2008.00467.x
Subject(s) - biology , schizosaccharomyces pombe , schizosaccharomyces , saccharomyces cerevisiae , biochemistry , microbiology and biotechnology , gene , genetics
Arsenic (As) and cadmium (Cd) are two of the most hazardous substances in the environment and have been implicated in a number of human diseases including cancer. Their mechanisms of toxicity and subsequent carcinogenesis are not understood. To identify the genes involved in As/Cd detoxification, we screened a random insertional mutagenesis library of Schizosaccharomyces pombe for mutants that are hypersensitive to As/Cd. Mutations were mapped to spc1 + ( sty1 + ) and SPBC17G9.08c . Spc1 is a stress‐activated protein kinase orthologous to human p38. A fragment of SPBC17G9.08c was previously identified as csx2 , a high‐copy suppressor of cut6 that encodes an acetyl‐CoA carboxylase involved in fatty acid biosynthesis. SPBC17G9.08c is a member of the centaurin ADP ribosylation factor GTPase activating protein family found in a variety of fungi, plants and metazoans, but not in Saccharomyces cerevisiae . Cnt5, so named because its closest human homolog is centaurin β‐5, binds to phosphatidic acid and phosphatidyl serine in vitro . Microscopic localization of Cnt5‐GFP indicates significant redistribution of Cnt5 from the cytoplasm to the cell membranes in response to As stress. These data suggest a model in which Cnt5 contributes to As/Cd resistance by maintaining membrane integrity or by modulating membrane trafficking.