TY - JOUR
T1 - Oxidant resistance in a yeast mutant deficient in the Sit4 phosphatase
AU - López-Mirabal, H Reynaldo
AU - Winther, Jakob R
AU - Kielland-Brandt, Morten C
N1 - Keywords: Actins; 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
PY - 2008
Y1 - 2008
N2 - 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).
AB - 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).
U2 - 10.1007/s00294-008-0184-z
DO - 10.1007/s00294-008-0184-z
M3 - Journal article
C2 - 18357452
VL - 53
SP - 275
EP - 286
JO - Current Genetics
JF - Current Genetics
SN - 0172-8083
IS - 5
ER -