Nucleoredoxin, glutaredoxin, and thioredoxin differentially regulate NF-kappaB, AP-1, and CREB activation in HEK293 cells.
Well-established mechanisms for regulation of protein activity include thiol-mediated oxidoreduction in addition to protein-protein interactions and phosphorylation. Nucleoredoxin (NRX), glutaredoxin (GRX), and thioredoxin (TRX) have been shown to act as a potent thiol reductase and reactive oxygen species regulator. They constitute a oxidoreductase superfamily and have been suggested as a candidate operating in the redox regulation of gene expression. We demonstrated here that intracellular localization of these redox molecules differ from each other and that the redox molecules differentially regulate NF-kappaB, AP-1, and CREB activation induced by TNFalpha, PMA, and forskolin and by expression of signaling intermediate kinases, NIK, MEKK, and PKA in HEK293 cells. This is a first report that describes involvement of NRX and GRX and differences from TRX in transcriptional regulation of NF-kappaB, AP-1, and CREB in living cells.
Hirota
K
K
Department of Anesthesia, Kyoto University Hospital, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-Ku, Kyoto, 606-8507, Japan. khirota@kuhp.kyoto-u.ac.jp
Matsui
M
M
Murata
M
M
Takashima
Y
Y
Cheng
F S
FS
Itoh
T
T
Fukuda
K
K
Yodoi
J
J
Junji
Y
Y
D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins; D019084:Fluorescent Antibody Technique, Indirect; D005656:Fungal Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D054477:Glutaredoxins; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013879:Thioredoxins / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; C516005:GLRX protein, human; D054477:Glutaredoxins; D016328:NF-kappa B; D009687:Nuclear Proteins; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D013879:Thioredoxins; D010088:Oxidoreductases; C105231:nucleoredoxin; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; C482578:Map3k1 protein, mouse; D013755:Tetradecanoylphorbol Acetate