Oxidant resistance in a yeast mutant deficient in the Sit4 phosphatase.

Resistance to thiol oxidation can arise from mutations altering redox homeostasis. A Saccharomyces cerevisiae sit4-110 mutant is here described, which was isolated as resistant to the thiol-specific oxidant dipyridyl disulfide (DPS) and which contains a single-residue substitution in the SIT4 gene. Sit4p is a protein phosphatase with multiple roles in ...
signal transduction through the target-of-rapamycin (TOR) pathway. We found that sit4-110 elevates the levels of glutathione. However, this cannot be the (only) cause for the DPS-resistance, since sit4-110 also conferred DPS/H2O2-resistance in a glutathione-deficient strain. Of the known Sit4p substrates, only Tip41p is involved in DPS-resistance; both Delta tip41 deletion and overexpression of the Tip41p target Tap42p resulted in increased DPS-resistance. Thus, the role of Sit4p in DPS-tolerance differs from its role during TOR-inactivation and salt stress. In view of Tap42p's known involvement in actin homeostasis, sit4-110 could compensate for putative actin-related defects caused by DPS. However, sit4-110 has pronounced actin polarization defects under both absence and presence of DPS. A relation between actin homeostasis and DPS resistance of sit4-110 cannot be ruled out, but our results suggest that unknown pathways might be involved in DPS resistance through mechanisms involving the Sit4p and/or Tap42p function(s).
Mesh Terms:
Actins, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Dehydration, Disulfides, Drug Resistance, Fungal, Glutathione, Intracellular Signaling Peptides and Proteins, Molecular Sequence Data, Mutation, Nitrogen, Oxidants, Oxidative Stress, Phosphoric Monoester Hydrolases, Protein Phosphatase 2, Pyridines, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Salts, Sequence Homology, Amino Acid
Curr. Genet.
Date: May. 01, 2008
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