Mammalian thioredoxin is a direct inhibitor of apoptosis signal‐regulating kinase (ASK) 1
Open accessAbstract
Apoptosis signal-regulating kinase (ASK) 1 was recently identified as a mitogen-activated protein (MAP) kinase kinase kinase which activates the c-Jun N-terminal kinase (JNK) and p38 MAP kinase pathways and is required for tumor necrosis factor (TNF)-alpha-induced apoptosis; however, the mechanism regulating ASK1 activity is unknown. Through genetic screening for ASK1-binding proteins, thioredoxin (Trx), a reduction/oxidation (redox)-regulatory protein thought to have anti-apoptotic effects, was identified as an interacting partner of ASK1. Trx associated with the N-terminal portion of ASK1 in vitro and in vivo. Expression of Trx inhibited ASK1 kinase activity and the subsequent ASK1-dependent apoptosis. Treatment of cells with N-acetyl-L-cysteine also inhibited serum withdrawal-, TNF-alpha- and hydrogen peroxide-induced activation of ASK1 as well as apoptosis. The interaction between Trx and ASK1 was found to be highly dependent on the redox status of Trx. Moreover, inhibition of Trx resulted in activation of endogenous ASK1 activity, suggesting that Trx is a physiological inhibitor of ASK1. The evidence that Trx is a negative regulator of ASK1 suggests possible mechanisms for redox regulation of the apoptosis signal transduction pathway as well as the effects of antioxidants against cytokine- and stress-induced apoptosis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Both thioredoxin and glutaredoxin have anti-apoptotic properties through interactions with transcription factors and proteins, such as inhibition of the MAPK cascade by binding to ASK-1 in their reduced state.
“Both redoxins are also known to have anti-apoptotic properties through interactions with several transcription factors and proteins, such as inhibition of the MAPK cascade by binding to ASK-1 in their reduced state24,35.”
From Inhibition of the glutaredoxin and thioredoxin systems and ribonucleotide reductase by mutant p53-targeting compound APR-246 (2018) · cites this paper as [24]
The Introduction and the section ‘Redox status-dependent interaction of Trx and ASK1’ report that reduced thioredoxin binds ASK1, inhibits its kinase activity and reduces ASK1-dependent apoptosis. The paper does not report that glutaredoxin binds ASK1 or inhibits this pathway; glutaredoxin appears only in a reference title. Page numbers were not supplied for these passages. (LLM, conf=0.88)
Experimental — accuracy not yet measuredLoss of free thiols in Trx1 leads to the release of ASK1, which activates JNK and p38 MAP kinase pathways and in turn TNF-α-induced apoptosis.
“Loss of free thiols in Trx1 leads to the release of ASK1, which activates the c-Jun N-terminal kinase (JNK) and p38 MAP kinase pathways and in turn TNF-α-induced apoptosis24.”
From Inhibition of the glutaredoxin and thioredoxin systems and ribonucleotide reductase by mutant p53-targeting compound APR-246 (2018) · cites this paper as [24]
The Redox status-dependent interaction section reports that reduced Trx binds ASK1 and that oxidation can disrupt the interaction; it also reports TNF-α-induced dissociation. The Introduction identifies ASK1 as an activator of JNK and p38 pathways. But the Conclusion presents oxidation-driven release of ASK1 as a proposed mechanism and says it remains unclear whether TNF-α activates ASK1 primarily through intracellular redox changes, so the claim states that causal sequence more definitively than the paper does. (LLM, conf=0.86)
Experimental — accuracy not yet measuredASK1 is inhibited by Trx through protein-protein interactions that maintain ASK1 in an inactive state.
“ASK1 is inhibited by Trx due to their protein–protein interactions that maintain ASK1 in an inactive state (365).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [365]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Apoptosis in the Pathogenesis and Treatment of Disease
Thompson, C. B. (1995) · Science · doi:10.1126/science.7878464 · Cited by 6,524 · see citing works
Smith, D. B., & Johnson, K. S. (1988) · Gene · doi:10.1016/0378-1119(88)90005-4 · Cited by 5,974 · see citing works
Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis
Xia, Z., Dickens, M., Raingeaud, J., Davis, R. J., & Greenberg, M. E. (1995) · Science · doi:10.1126/science.270.5240.1326 · Cited by 5,290 · see citing works
H2O2 from the oxidative burst orchestrates the plant hypersensitive disease resistance response
Levine, A., Tenhaken, R., Dixon, R. A., & Lamb, C. J. (1994) · Cell · doi:10.1016/0092-8674(94)90544-4 · Cited by 2,767 · see citing works
Mechanisms and Genes of Cellular Suicide
Steller, H. (1995) · Science · doi:10.1126/science.7878463 · Cited by 2,465 · see citing works
Ichijo, H., Nishida, E., Irie, K., ten Dijke, P., Saitoh, M., Moriguchi, T., Takagi, M., Matsumoto, K., Miyazono, K., & Gotoh, Y. (1997) · Science · doi:10.1126/science.275.5296.90 · Cited by 2,310 · see citing works
Self-citationRaingeaud, J., Gupta, S., Rogers, J. S., Dickens, M., Han, J., Ulevitch, R. J., & Davis, R. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7420 · Cited by 2,244 · see citing works
Oxidative stress as a mediator of apoptosis
Buttke, T. M., & Sandstrom, P. A. (1994) · Immunology Today · doi:10.1016/0167-5699(94)90018-3 · Cited by 2,149 · see citing works
Caspases: Intracellular Signaling by Proteolysis
Salvesen, G. S., & Dixit, V. M. (1997) · Cell · doi:10.1016/s0092-8674(00)80430-4 · Cited by 2,133 · see citing works
The TNF receptor 1-associated protein TRADD signals cell death and NF-κB activation
Hsu, H., Xiong, J., & Goeddel, D. V. (1995) · Cell · doi:10.1016/0092-8674(95)90070-5 · Cited by 2,024 · see citing works
Holmgren, A. (1985) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.54.070185.001321 · Cited by 1,955 · see citing works
Thioredoxin and Glutaredoxin Systems
Holmgren, A. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)71625-6 · Cited by 1,804 · see citing works
Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis
Verheij, M., Bose, R., Lin, X. H., Yao, B., Jarvis, W. D., Grant, S., Birrer, M. J., Szabo, E. M., Zon, L. I., Kyriakis, J. M., et al. (1996) · Nature · doi:10.1038/380075a0 · Cited by 1,767 · see citing works
Mitogenic Signaling Mediated by Oxidants in Ras-Transformed Fibroblasts
Irani, K., Xia, Y., Zweier, J. L., Sollott, S. J., Der, C. J., Fearon, E. R., Sundaresan, M., Finkel, T., & Goldschmidt-Clermont, P. J. (1997) · Science · doi:10.1126/science.275.5306.1649 · Cited by 1,588 · see citing works
Mitochondrial control of apoptosis
Kroemer, G., Zamzami, N., & Susín, S. A. (1997) · Immunology Today · doi:10.1016/s0167-5699(97)80014-x · Cited by 1,492 · see citing works
REDOX REGULATION OF CELLULAR ACTIVATION
Nakamura, H., Nakamura, K., & Yodoi, J. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.351 · Cited by 1,106 · see citing works
The MAP kinase cascade is essential for diverse signal transduction pathways
Nishida, E., & Gotoh, Y. (1993) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(93)90019-j · Cited by 1,087 · see citing works
MAP kinase kinase kinase, MAP kinase kinase and MAP kinase
Marshall, C. J. (1994) · Current Opinion in Genetics & Development · doi:10.1016/0959-437x(94)90095-7 · Cited by 1,005 · see citing works
MAPKs: new JNK expands the group
Davis, R. J. (1994) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(94)90132-5 · Cited by 944 · see citing works
AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1
Hirota, K., Matsui, M., Iwata, S., Nishiyama, A., Mori, K., & Yodoi, J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3633 · Cited by 845 · see citing works
Miyake, S., Makimura, M., Kanegae, Y., Harada, S., Sato, Y., Takamori, K., Tokuda, C., & Saito, I. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.3.1320 · Cited by 788 · see citing works
Reactive oxygen species and programmed cell death
Jacobson, M. D. (1996) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(96)20008-8 · Cited by 753 · see citing works
Protein kinase cascades activated by stress and inflammatory cytokines
Kyriakis, J. M., & Avruch, J. (1996) · BioEssays · doi:10.1002/bies.950180708 · Cited by 709 · see citing works
Meier, B., Radeke, H. H., Selle, S., Younes, M., Sies, H., Resch, K., & Habermehl, G. (1989) · Biochemical Journal · doi:10.1042/bj2630539 · Cited by 650 · see citing works
Waskiewicz, A. J., & Cooper, J. A. (1995) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(95)80063-8 · Cited by 575 · see citing works
Tagaya, Y., Maeda, Y., Mitsui, A., Kondo, N., Matsui, H., Hamuro, J., Brown, N., Arai, K., Yokota, T., & Wakasugi, H. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb03436.x · Cited by 562 · see citing works
Early Embryonic Lethality Caused by Targeted Disruption of the Mouse Thioredoxin Gene
Matsui, M., Oshima, M., Oshima, H., Takaku, K., Maruyama, T., Yodoi, J., & Taketo, M. M. (1996) · Developmental Biology · doi:10.1006/dbio.1996.0208 · Cited by 546 · cited 1× · see citing works
“Trx is required for negative regulation of ASK1 in vivo A targeted disruption of mouse Trx gene has recently been reported (Matsui et al., 1996).”
BackgroundLo, Y. Y. C., & Cruz, T. F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.20.11727 · Cited by 530 · see citing works
Hayashi, T., Ueno, Y., & Okamoto, T. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82135-4 · Cited by 489 · see citing works
Chiang, M. Y.-N., Chan, H., Zounes, M. A., Freier, S., Lima, W. F., & Bennett, C. F. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)55250-9 · Cited by 463 · see citing works
Ohba, M., Shibanuma, M., Kuroki, T., & Nose, K. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.126.4.1079 · Cited by 462 · see citing works
Holmgren, A. (1995) · Structure · doi:10.1016/s0969-2126(01)00153-8 · Cited by 437 · see citing works
Mayer, M., & Noble, M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.16.7496 · Cited by 371 · see citing works
Structural and functional relations among thioredoxins of different species
Eklund, H., Gleason, F. K., & Holmgren, A. (1991) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340110103 · Cited by 367 · see citing works
Cuenda, A., Cohen, P., Buée‐Scherrer, V., & Goedert, M. (1997) · The EMBO Journal · doi:10.1093/emboj/16.2.295 · Cited by 362 · see citing works
Takeuchi, K., Sato, N., Kasahara, H., Funayama, N., Nagafuchi, A., Yonemura, S., Tsukita, S., & Tsukita, S. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.125.6.1371 · Cited by 348 · see citing works
MEKKs, GCKs, MLKs, PAKs, TAKs, and Tpls: upstream regulators of the c-Jun amino-terminal kinases?
Fanger, G. R., Gerwins, P., Widmann, C., Jarpe, M. B., & Johnson, G. L. (1997) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(97)80111-6 · Cited by 317 · see citing works
Cossarizza, A., Franceschi, C., Monti, D., Salvioli, S., Bellesia, E., Rivabene, R., Biondo, L. A., Rainaldi, G., Tinari, A., & Malorni, W. (1995) · Experimental Cell Research · doi:10.1006/excr.1995.1311 · Cited by 273 · see citing works
A conserved kinase cascade for MAP kinase activation in yeast
Errede, B., & Levin, D. E. (1993) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(93)90112-4 · Cited by 251 · see citing works
Nakamura, H., Matsuda, M., Furuke, K., Kitaoka, Y., Iwata, S., Toda, K., Inamoto, T., Yamaoka, Y., Ozawa, K., & Yodoi, J. (1994) · Immunology Letters · doi:10.1016/0165-2478(94)90038-8 · Cited by 248 · see citing works
Matthews, N., Neale, M. L., Jackson, S. K., & Stark, J. M. (1987) · PubMed Central · Cited by 204 · see citing works
Sasada, T., Iwata, S., Sato, N., Kitaoka, Y., Hirota, K., Nakamura, K., Nishiyama, A., Taniguchi, Y., Takabayashi, A., & Yodoi, J. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118668 · Cited by 201 · see citing works
Matsuda, M., Masutani, H., Nakamura, H. K., Miyajima, S., Yamauchi, A., Yonehara, S., Uchida, A., Irimajiri, K., Horiuchi, A., & Yodoi, J. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.147.11.3837 · Cited by 200 · see citing works
Yamauchi, N., Kuriyama, H., Watanabe, N., Neda, H., Maeda, M., & Niitsu, Y. (1989) · PubMed · Cited by 199 · see citing works
Kawabata, M., Chytil, A., & Moses, H. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.10.5625 · Cited by 189 · see citing works
Self-citation1-Chloro-2,4-dinitrobenzene Is an Irreversible Inhibitor of Human Thioredoxin Reductase
Arnér, E. S. J., Björnstedt, M., & Holmgren, A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.8.3479 · Cited by 187 · see citing works
Mitsui, A., Hírakawa, T., & Yodoi, J. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(05)81536-0 · Cited by 176 · see citing works
Makino, Y., Okamoto, K., Yoshikawa, N., Aoshima, M., Hirota, K., Yodoi, J., Umesono, K., Makino, I., & Tanaka, H. (1996) · Journal of Clinical Investigation · doi:10.1172/jci119065 · Cited by 172 · see citing works
Kretsinger, R. H., Uversky, V. N., & Permyakov, E. A. (2013) · Springer eBooks · doi:10.1007/978-1-4614-1533-6_100926 · Cited by 164 · see citing works
Gallegos, A. C., Gasdaska, J. R., Taylor, C. W., Paine-Murrieta, G. D., Goodman, D., Gasdaska, P. Y., Berggren, M. I., Briehl, M. M., & Powis, G. (1996) · PubMed · Cited by 161 · see citing works
Saito, I., Oya, Y., Yamamoto, K., Yuasa, T., & Shimojo, H. (1985) · Journal of Virology · doi:10.1128/jvi.54.3.711-719.1985 · Cited by 147 · see citing works
Bulkley, G. B. (1994) · The Lancet · doi:10.1016/s0140-6736(94)92276-4 · Cited by 131 · see citing works
Oblong, J. E., Berggren, M. I., Gasdaska, P., et al. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32631-5 · Cited by 120 · see citing works
Thioredoxin: A Multifunctional Regulatory Protein with a Bright Future in Technology and Medicine
Buchanan, B. B., Schürmann, P., Decottignies, P., et al. (1994) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1994.1439 · Cited by 118 · see citing works
Satoh, T., Sakai, N., Enokido, Y., Uchiyama, Y., & Hatanaka, H. (1996) · Brain Research · doi:10.1016/0006-8993(96)00527-6 · Cited by 114 · see citing works
Tanaka, T., Nishiyama, Y., Okada, K., et al. (1997) · PubMed · Cited by 104 · see citing works
Satoh, T. (1996) · Brain Research · doi:10.1016/s0006-8993(96)00527-6 · Cited by 102 · see citing works
Molecular Cloning and Characterization of the Mouse Apoptosis Signal-Regulating Kinase 1
Tobiume, K., Inage, T., Takeda, K., et al. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7580 · Cited by 75 · see citing works
Self-citationApoptosis: Telling cells their time is up
Nagata, S. (1996) · Current Biology · doi:10.1016/s0960-9822(02)70706-9 · Cited by 73 · see citing works
Novogrodsky, A., Nehring, R. E., & Meister, A. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.10.4932 · Cited by 37 · see citing works
Tagaya, Y., Maeda, Y., Mitsui, A., et al. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06502.x · Cited by 23 · see citing works
Nakamura, H., Matsuda, M., Furuke, K., et al. (1994) · Immunology Letters · doi:10.1016/0165-2478(94)90090-6 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Free Radicals in the Physiological Control of Cell Function
Dröge, W. (2002) · Physiological Reviews · doi:10.1152/physrev.00018.2001 · Cited by 9,855 · see citing works
Oxidants, oxidative stress and the biology of ageing
Finkel, T., & Holbrook, N. J. (2000) · Nature · doi:10.1038/35041687 · Cited by 9,413 · see citing works
Role of nrf2 in oxidative stress and toxicity
Ma, Q. (2013) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140320 · Cited by 4,903 · see citing works
Oxyl radicals, redox-sensitive signalling cascades and antioxidants
Genestra, M. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.04.009 · Cited by 4,930 · see citing works
Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling
Ray, P. D., Huang, B.-W., & Tsuji, Y. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.01.008 · Cited by 4,373 · see citing works
Crosstalk of reactive oxygen species and NF-κB signaling
Morgan, M. J., & Liu, Z.-G. (2011) · Cell Research · doi:10.1038/cr.2010.178 · Cited by 3,505 · see citing works
Reactive oxygen species, cellular redox systems, and apoptosis
Circu, M. L., & Aw, T. Y. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.12.022 · Cited by 3,340 · see citing works
Signal transduction by reactive oxygen species
Finkel, T. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102095 · Cited by 2,322 · see citing works
Redox regulation of cell survival
Trachootham, D., Lu, W., Ogasawara, M. A., Valle, N. R.-D., & Huang, P. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1957 · Cited by 1,781 · see citing works
Hydrogen peroxide sensing and signaling
Veal, E. A., Day, A. M., & Morgan, B. A. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.03.016 · Cited by 1,604 · see citing works
Selenium in human health and disease
Fairweather-Tait, S. J., Bao, Y., Broadley, M. R., Collings, R., Ford, D., Hesketh, J. E., & Hurst, R. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3275 · Cited by 1,330 · see citing works
Thiol chemistry and specificity in redox signaling
Winterbourn, C. C., & Hampton, M. B. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.05.004 · Cited by 1,226 · see citing works
Radical-free biology of oxidative stress
Jones, D. P. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00283.2008 · Cited by 1,213 · see citing works
TNF and ROS crosstalk in inflammation
Blaser, H., Dostert, C., Mak, T. W., & Brenner, D. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.12.002 · Cited by 1,008 · see citing works
Kregel, K. C., & Zhang, H. J. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00327.2006 · Cited by 883 · see citing works
Reactive oxygen species and cell signaling: Respiratory burst in macrophage signaling
Forman, H. J., & Torres, M. (2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.2206007 · Cited by 891 · see citing works
Tebay, L. E., Robertson, H., Durant, S. T., Vitale, S. R., Penning, T. M., Dinkova-Kostova, A. T., & Hayes, J. D. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.06.021 · Cited by 837 · see citing works
Signaling Functions of Reactive Oxygen Species
Forman, H. J., Maiorino, M., & Ursini, F. (2010) · Biochemistry · doi:10.1021/bi9020378 · Cited by 827 · see citing works
[11] Redox potential of GSH/GSSG couple: Assay and biological significance
Jones, D. P. (2002) · Methods in Enzymology · doi:10.1016/s0076-6879(02)48630-2 · Cited by 812 · see citing works
Redox-based regulation of signal transduction: principles, pitfalls, and promises
Janssen-Heininger, Y. M. W., Mossman, B. T., Heintz, N. H., Forman, H. J., Kalyanaraman, B., Finkel, T., Stamler, J. S., Rhee, S. G., & van der Vliet, A. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.03.011 · Cited by 784 · see citing works
Thioredoxin and Related Molecules–From Biology to Health and Disease
Lillig, C. H., & Holmgren, A. (2007) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.9.25 · Cited by 724 · see citing works
Matsuzawa, A., Saegusa, K., Noguchi, T., Sadamitsu, C., Nishitoh, H., Nagai, S., Koyasu, S., Matsumoto, K., Takeda, K., & Ichijo, H. (2005) · Nature Immunology · doi:10.1038/ni1200 · Cited by 667 · see citing works
Self-citationRedox regulation of mitochondrial function
Handy, D. E., & Loscalzo, J. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4123 · Cited by 588 · see citing works
The Two Faces of Reactive Oxygen Species in Cancer
Reczek, C. R., & Chandel, N. S. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-041916-065808 · Cited by 602 · see citing works
“…oxidation of TRX causes ASK1 dissociation and activation, thereby triggering the suppression of anti-apoptotic factors through the sustained activation of the downstream MAP kinase kinase (MKK)4/MKK7/JNK and MKK3/MKK6/p38 pathways (Ichijo et al. 1997, Saitoh et al. 1998, Tobiume et al. 2001).”
BackgroundRedox signaling and the MAP kinase pathways
Torres, M., & Forman, H. J. (2003) · BioFactors · doi:10.1002/biof.5520170128 · Cited by 580 · see citing works
Alcohol and mitochondria: a dysfunctional relationship
Hoek, J. B., Cahill, A., & Pastorino, J. G. (2002) · Gastroenterology · doi:10.1053/gast.2002.33613 · Cited by 553 · see citing works
ROS in Cancer: The Burning Question
Chio, I. I. C., & Tuveson, D. A. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.03.004 · Cited by 532 · see citing works
Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species
Bashan, N., Kovsan, J., Kachko, I., Ovadia, H., & Rudich, A. (2009) · Physiological Reviews · doi:10.1152/physrev.00014.2008 · Cited by 542 · see citing works
Molecular Mechanisms and Clinical Implications of Reversible Protein <i>S</i> -Glutathionylation
Mieyal, J. J., Gallogly, M. M., Qanungo, S., Sabens, E. A., & Shelton, M. D. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2089 · Cited by 523 · see citing works
Hanawa, N., Shinohara, M., Saberi, B., Gaarde, W. A., Han, D., & Kaplowitz, N. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708916200 · Cited by 527 · see citing works
Thioredoxin Reductase Is Irreversibly Modified by Curcumin
Fang, J., Lu, J., & Holmgren, A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414645200 · Cited by 521 · see citing works
Sakon, S., Xue, X., Takekawa, M., Sasazuki, T., Okazaki, T., Kojima, Y., Piao, J., Yagita, H., Okumura, K., Doi, T., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg379 · Cited by 497 · see citing works
C-Jun N-terminal kinase plays a major role in murine acetaminophen hepatotoxicity
Gunawan, B. K., Liu, Z., Han, D., Hanawa, N., Gaarde, W. A., & Kaplowitz, N. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.03.045 · Cited by 471 · see citing works
Redox-Directed Cancer Therapeutics: Molecular Mechanisms and Opportunities
Wondrak, G. T. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2541 · Cited by 462 · see citing works
Targeting the Thioredoxin System for Cancer Therapy
Zhang, J., Li, X., Han, X., Liu, R., & Fang, J. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.06.001 · Cited by 460 · see citing works
Oxidative Stress, Chronic Disease, and Muscle Wasting
Moylan, J. S., & Reid, M. B. (2007) · Muscle & Nerve · doi:10.1002/mus.20743 · Cited by 416 · see citing works
Nishikawa, T., & Araki, E. (2007) · Antioxidants & Redox Signaling · doi:10.1089/ars.2006.1458 · Cited by 391 · see citing works
Thomas, S. R., Witting, P. K., & Drummond, G. R. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2027 · Cited by 383 · see citing works
The ASK1-MAP Kinase Cascades in Mammalian Stress Response
Matsukawa, J. (2004) · Journal of Biochemistry · doi:10.1093/jb/mvh134 · Cited by 343 · see citing works
Lu, J., Papp, L. V., Fang, J., Rodriguez-Nieto, S., Zhivotovsky, B., & Holmgren, A. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3310 · Cited by 326 · see citing works
Mechanisms of drug-induced liver injury
Yuan, L., & Kaplowitz, N. (2013) · Clinics in Liver Disease · doi:10.1016/j.cld.2013.07.002 · Cited by 322 · see citing works
Redox regulation of protein kinases
Corcoran, A., & Cotter, T. G. (2013) · The FEBS Journal · doi:10.1111/febs.12224 · Cited by 306 · see citing works
Oxidative Stress Responses in the Human Fungal Pathogen, Candida albicans
Dantas, A., Day, A., Ikeh, M., Kos, I., Achan, B., & Quinn, J. (2015) · Biomolecules · doi:10.3390/biom5010142 · Cited by 281 · see citing works
Thioredoxin System in Cell Death Progression
Lu, J., & Holmgren, A. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4650 · Cited by 279 · see citing works
Shao, D., Oka, S.-I., Liu, T., Zhai, P., Ago, T., Sciarretta, S., Li, H., & Sadoshima, J. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.013 · Cited by 252 · see citing works
Phosphorylation and Inactivation of Myeloid Cell Leukemia 1 by JNK in Response to Oxidative Stress
Inoshita, S., Takeda, K., Hatai, T., Terada, Y., Sano, M., Hata, J., Umezawa, A., & Ichijo, H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207951200 · Cited by 233 · see citing works
Self-citationThe chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal
Forman, H. J., Fukuto, J. M., Miller, T., Zhang, H., Rinna, A., & Levy, S. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.06.011 · Cited by 226 · see citing works
Molecular Mechanisms and Genetics of Oxidative Stress in Alzheimer’s Disease
Cioffi, F., Adam, R. H. I., & Broersen, K. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190863 · Cited by 204 · see citing works
“apoptosis signal-regulating kinase-1 (Ask-1) [253].”
Redox signaling: an evolution from free radicals to aging
Forman, H. J. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.07.003 · Cited by 172 · see citing works
Yokoi, T., Fukuo, K., Yasuda, O., Hotta, M., Miyazaki, J., Takemura, Y., Kawamoto, H., Ichijo, H., & Ogihara, T. (2006) · Diabetes · doi:10.2337/db05-1607 · Cited by 169 · see citing works
Self-citationSelenius, M., Rundlöf, A.-K., Olm, E., Fernandes, A. P., & Björnstedt, M. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2884 · Cited by 170 · see citing works
Thioredoxin and Thioredoxin Reductase in Relation to Reversible <i>S</i> -Nitrosylation
Sengupta, R., & Holmgren, A. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4716 · Cited by 156 · see citing works
Hou, N., Torii, S., Saito, N., Hosaka, M., & Takeuchi, T. (2008) · Endocrinology · doi:10.1210/en.2007-0988 · Cited by 141 · see citing works
Pharmacological antioxidant strategies as therapeutic interventions for COPD
Rahman, I. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.11.004 · Cited by 117 · see citing works
The role of thioredoxin in the regulation of cellular processes by S-nitrosylation
Sengupta, R., & Holmgren, A. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.08.012 · Cited by 110 · see citing works
Griffiths, H. R. (2005) · Redox Report · doi:10.1179/135100005x83680 · Cited by 103 · see citing works
Haffo, L., Lu, J., Bykov, V. J. N., Martin, S. S., Ren, X., Coppo, L., Wiman, K. G., & Holmgren, A. (2018) · Scientific Reports · doi:10.1038/s41598-018-31048-7 · Cited by 73 · see citing works
Sumbayev, V. V. (2008) · FEBS Letters · doi:10.1016/j.febslet.2007.12.024 · Cited by 62 · see citing works
The role of mitochondria in <scp>mTOR</scp>‐regulated longevity
Wei, Y., Zhang, Y., Cai, Y., & Xu, M. (2015) · Biological Reviews · doi:10.1111/brv.12103 · Cited by 56 · see citing works
MiR-23-TrxR1 as a novel molecular axis in skeletal muscle differentiation
Mercatelli, N., Fittipaldi, S., De Paola, E., Dimauro, I., Paronetto, M. P., Jackson, M. J., & Caporossi, D. (2017) · Scientific Reports · doi:10.1038/s41598-017-07575-0 · Cited by 49 · see citing works
Jones, D. T., Pugh, C. W., Wigfield, S., Stevens, M. F. G., & Harris, A. L. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2380 · Cited by 48 · see citing works
Targeting NF-κB and HIF-1 Pathways for the Treatment of Cancer: Part II
Wilczynski, J., Duechler, M., & Czyz, M. (2011) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-011-0132-3 · Cited by 41 · see citing works
New insights into redox homeostasis as a therapeutic target in B-cell malignancies
Graczyk-Jarzynka, A., Zagozdzon, R., Muchowicz, A., Siernicka, M., Juszczynski, P., & Firczuk, M. (2017) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000351 · Cited by 29 · see citing works
- Authors
- Saitoh, M., Nishitoh, H., Fujii, M., Takeda, K., Tobiume, K., Sawada, Y., Kawabata, M., Miyazono, K., & Ichijo, H.
- Affiliations
- Japanese Foundation For Cancer Research (JP)
- Tokyo Medical and Dental University (JP)
- Corresponding author
- Saitoh, Masao
- Venue
- The EMBO Journal
- Published
- 1998-05-01
- Volume
- 17
- Issue
- 9
- Pages
- 2596-2606
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1170601
- OpenAlex
- W1969268163
- Cited by
- 2,377
- References
- 62
- Citations by year
- 2026: 26 · 2025: 24 · 2024: 32 · 2023: 47 · 2022: 59 · 2021: 70 · 2020: 60 · 2019: 65 · 2018: 67 · 2017: 99 · 2016: 81 · 2015: 94 · 2014: 104 · 2013: 86 · 2012: 123
- FWCI
- 23.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- thioredoxin, ASK1, MAP kinase kinase kinase, redox regulation, protein-protein interaction, kinase inhibition, TNF-induced apoptosis, N-acetylcysteine, antioxidants, c-Jun N-terminal kinase, p38 MAPK, hydrogen peroxide, serum deprivation
- MeSH terms
- Animals, Brain, Cell Line, Chlorides, Enzyme Activation, Enzyme Inhibitors, Humans, Hydrogen Peroxide, L Cells, Mammals, Oxidation-Reduction, Recombinant Proteins, Thioredoxins, Transfection, Tumor Necrosis Factor-alpha, Signal Transduction, Culture Media, Serum-Free, Apoptosis, Protein Serine-Threonine Kinases, Zinc Compounds, MAP Kinase Kinase Kinases, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
