Differential roles of tau class glutathione S-transferases in oxidative stress

TY - JOUR

T1 - Differential roles of tau class glutathione S-transferases in oxidative stress

AU - Kilili, Kimiti G

AU - Atanassova, Neli

AU - Vardanyan, Alla

AU - Clatot, Nicolas

AU - Al-Sabarna, Khaled

AU - Kanellopoulos, Panagiotis N

AU - Makris, Antonios M

AU - Kampranis, Sotirios C

PY - 2004/6/4

Y1 - 2004/6/4

N2 - The plant glutathione S-transferase BI-GST has been identified as a potent inhibitor of Bax lethality in yeast, a phenotype associated with oxidative stress and disruption of mitochondrial functions. Screening of a tomato two-hybrid library for BI-GST interacting proteins identified five homologous Tau class GSTs, which readily form heterodimers between them and BI-GST. All six LeGSTUs were found to be able to protect yeast cells from prooxidant-induced cell death. The efficiency of each LeGSTU was prooxidant-specific, indicating a different role for each LeGSTU in the oxidative stress-response mechanism. The prooxidant protective effect of all six proteins was suppressed in the absence of YAP1, a transcription factor that regulates hydroperoxide homeostasis in Saccharomyces cerevisiae, suggesting a role for the LeGSTUs in the context of the YAP1-dependent stress-responsive machinery. The different LeGSTUs exhibited varied substrate specificity and showed activity against oxidative stress by-products, indicating that their prooxidant protective function is likely related to the minimization of oxidative damage. Taken together, these results indicate that Tau class GSTs participate in a broad network of catalytic and regulatory functions involved in the oxidative stress response.

AB - The plant glutathione S-transferase BI-GST has been identified as a potent inhibitor of Bax lethality in yeast, a phenotype associated with oxidative stress and disruption of mitochondrial functions. Screening of a tomato two-hybrid library for BI-GST interacting proteins identified five homologous Tau class GSTs, which readily form heterodimers between them and BI-GST. All six LeGSTUs were found to be able to protect yeast cells from prooxidant-induced cell death. The efficiency of each LeGSTU was prooxidant-specific, indicating a different role for each LeGSTU in the oxidative stress-response mechanism. The prooxidant protective effect of all six proteins was suppressed in the absence of YAP1, a transcription factor that regulates hydroperoxide homeostasis in Saccharomyces cerevisiae, suggesting a role for the LeGSTUs in the context of the YAP1-dependent stress-responsive machinery. The different LeGSTUs exhibited varied substrate specificity and showed activity against oxidative stress by-products, indicating that their prooxidant protective function is likely related to the minimization of oxidative damage. Taken together, these results indicate that Tau class GSTs participate in a broad network of catalytic and regulatory functions involved in the oxidative stress response.

KW - Amino Acid Sequence

KW - Catalysis

KW - Dimerization

KW - Dose-Response Relationship, Drug

KW - Glutathione

KW - Glutathione Disulfide

KW - Glutathione Transferase

KW - Hydrogen-Ion Concentration

KW - Kinetics

KW - Lycopersicon esculentum

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Oxidants

KW - Oxidative Stress

KW - Phenotype

KW - Precipitin Tests

KW - Protein Binding

KW - Protein Structure, Secondary

KW - Proto-Oncogene Proteins

KW - Proto-Oncogene Proteins c-bcl-2

KW - Saccharomyces cerevisiae

KW - Sequence Homology, Amino Acid

KW - Substrate Specificity

KW - Two-Hybrid System Techniques

KW - bcl-2-Associated X Protein

U2 - 10.1074/jbc.M309882200

DO - 10.1074/jbc.M309882200

M3 - Journal article

C2 - 15037622

SN - 0021-9258

VL - 279

SP - 24540

EP - 24551

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 23

ER -