Redox Regulation of Forkhead Proteins Through a p66shc -Dependent Signaling Pathway
Abstract
Genetic determinants of longevity include the forkhead-related transcription factor DAF-16 in the worm Caenorhabditis elegans and the p66shc locus in mice. We demonstrate that p66shc regulates intracellular oxidant levels in mammalian cells and that hydrogen peroxide can negatively regulate forkhead activity. In p66shc-/- cells, the activity of the mammalian forkhead homolog FKHRL1 is increased and redox-dependent forkhead inactivation is reduced. In addition, expression of FKHRL1 results in an increase in both hydrogen peroxide scavenging and oxidative stress resistance. These results demonstrate an important functional relation between three distinct elements linked to aging: forkhead proteins, p66shc, and intracellular oxidants.
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Cites
1 retracted
A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants
Taub, J. J., Lau, J. F., Ma, C., Hahn, J. H., Hoque, R., Rothblatt, J. A., & Chalfie, M. (1999) · Nature · doi:10.1038/20208 · Cited by 243 · see citing works
RetractedOxidants, 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
Self-citationAkt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor
Brunet, A., Bonni, A., Zigmond, M. J., Lin, M. Z., Juo, P., Hu, L. S., Anderson, M. J., Arden, K. C., Blenis, J., & Greenberg, M. E. (1999) · Cell · doi:10.1016/s0092-8674(00)80595-4 · Cited by 6,535 · see citing works
The p66shc adaptor protein controls oxidative stress response and life span in mammals
Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Pandolfi, P. P., Lanfrancone, L., & Pelicci, P. G. (1999) · Nature · doi:10.1038/46311 · Cited by 1,712 · see citing works
AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1
Medema, R. H., Kops, G. J. P. L., Bos, J. L., & Burgering, B. M. T. (2000) · Nature · doi:10.1038/35008115 · Cited by 1,439 · see citing works
Biggs, W., Meisenhelder, J., Hunter, T. R., Cavenee, W. K., & Arden, K. C. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.13.7421 · Cited by 1,116 · see citing works
Direct control of the Forkhead transcription factor AFX by protein kinase B
Kops, G. J. P. L., de Ruiter, N. D., de Vries-Smits, A. M. M., Powell, D. R., Bos, J. L., & Burgering, B. M. T. (1999) · Nature · doi:10.1038/19328 · Cited by 1,085 · see citing works
Henderson, S. T., & Johnson, T. E. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00594-2 · Cited by 949 · see citing works
Brunet, A., Park, J., Tran, H., Hu, L. S., Hemmings, B. A., & Greenberg, M. E. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.3.952-965.2001 · Cited by 860 · see citing works
Negative Regulation of the Forkhead Transcription Factor FKHR by Akt
Tang, E., Núñez, G., Barr, F. G., & Guan, K. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.24.16741 · Cited by 761 · see citing works
Honda, Y., & Honda, S. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.11.1385 · Cited by 730 · see citing works
Furuyama, T., Nakazawa, T., Nakano, I., & Mori, N. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3490629 · Cited by 672 · see citing works
Lee, R., Hench, J., & Ruvkun, G. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00595-4 · Cited by 508 · see citing works
Furuyama, T., Nakazawa, T., Nakano, I., et al. (2000) · Biochemical Journal · doi:10.1042/bj3490629 · Cited by 505 · see citing works
Longevity and heavy metal resistance in daf‐2 and age‐1 long‐lived mutants of Caenorhabditis elegans
Barsyte, D., Lovejoy, D. A., & Lithgow, G. J. (2001) · The FASEB Journal · doi:10.1096/fj.99-0966com · Cited by 270 · see citing works
Sonoda, Y., Watanabe, S., Matsumoto, Y., Aizu-Yokota, E., & Kasahara, T. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.15.10566 · Cited by 245 · see citing works
Regulation of nuclear translocation of Forkhead transcription factor AFX by protein kinase B
Takaishi, H., Konishi, H., Matsuzaki, H., Ono, Y., Shirai, Y., Saito, N., Kitamura, T., Ogawa, W., Kasuga, M., Kikkawa, U., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.21.11836 · Cited by 236 · see citing works
Zheng, W., Kar, S., & Quirion, R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002417200 · Cited by 152 · see citing works
Oxidative Stress-induced Phospholipase C-γ1 Activation Enhances Cell Survival
Wang, X., McCullough, K. D., Wang, X.-J., Carpenter, G. F., & Holbrook, N. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102693200 · Cited by 150 · see citing works
Murakami, S., & Johnson, T. E. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00453-5 · Cited by 82 · see citing works
Oxidative Preconditioning and Apoptosis in L-cells
Han, H. J., Wang, H., Long, H., Nattel, S., & Wang, Z. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011136200 · Cited by 79 · see citing works
Salinas, M., Martı́n, D., Alvarez, A. M., et al. (2001) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2000.0921 · Cited by 55 · see citing works
Activation of the Ras-related GTPase Rap1 by thymocyte TCR engagement and during selection
(2000) · Pure Amsterdam UMC · doi:10.1002/1521-4141(200010)30:10 · Cited by 3 · see citing works
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Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388 · see citing works
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Yalcin, S., Zhang, X., Luciano, J. P., Mungamuri, S. K., Marinkovic, D., Vercherat, C., Sarkar, A., Grisotto, M., Taneja, R., & Ghaffari, S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800517200 · Cited by 247 · see citing works
Camici, G. G., Schiavoni, M., Francia, P., Bachschmid, M., Martin-Padura, I., Hersberger, M., Tanner, F. C., Pelicci, P., Volpe, M., Anversa, P., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609656104 · Cited by 249 · see citing works
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Guidotti, G., Calabrese, F., Anacker, C., Racagni, G., Pariante, C. M., & Riva, M. A. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.225 · Cited by 200 · see citing works
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Mei, Y., Zhang, Y., Yamamoto, K., Xie, W., Mak, T. W., & You, H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0901104106 · Cited by 172 · see citing works
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The retardation of aging by caloric restriction: its significance in the transgenic era
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Vijg, J., & Suh, Y. (2005) · Annual Review of Medicine · doi:10.1146/annurev.med.56.082103.104617 · Cited by 142 · see citing works
FOXO3A regulates peroxiredoxin III expression in human cardiac fibroblasts
Chiribau, C. B., Cheng, L., Cucoranu, I. C., Yu, Y.-S., Clempus, R. E., & Sorescu, D. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m710610200 · Cited by 140 · see citing works
Xiao, G., Chan, L. N., Klemm, L., Braas, D., Chen, Z., Geng, H., Zhang, Q. C., Aghajanirefah, A., Cosgun, K. N., Sadras, T., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.048 · Cited by 129 · see citing works
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de Keizer, P. L. J., Burgering, B. M. T., & Dansen, T. B. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3403 · Cited by 131 · see citing works
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Migliaccio, E., Giorgio, M., & Pelicci, P. G. (2006) · Antioxidants & Redox Signaling · doi:10.1089/ars.2006.8.600 · Cited by 123 · see citing works
Corton, J. C., & Brown-Borg, H. M. (2005) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/60.12.1494 · Cited by 106 · see citing works
Loss of TIMP3 underlies diabetic nephropathy via FoxO1/STAT1 interplay
Fiorentino, L., Cavalera, M., Menini, S., Marchetti, V., Mavilio, M., Fabrizi, M., Conserva, F., Casagrande, V., Menghini, R., Pontrelli, P., et al. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201201475 · Cited by 98 · see citing works
de Keizer, P. L. J., Packer, L. M., Szypowska, A. A., Riedl-Polderman, P. E., van den Broek, N. J. F., de Bruin, A., Dansen, T. B., Marais, R., Brenkman, A. B., & Burgering, B. M. T. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1563 · Cited by 94 · see citing works
Hwang, I., Uchida, H., Dai, Z., Li, F., Sanchez, T., Locasale, J. W., Cantley, L. C., Zheng, H., & Paik, J. (2021) · Nature Communications · doi:10.1038/s41467-020-20839-0 · Cited by 61 · see citing works
Franzeck, F. C., Hof, D., Spescha, R. D., Hasun, M., Akhmedov, A., Steffel, J., Shi, Y., Cosentino, F., Tanner, F. C., von Eckardstein, A., et al. (2012) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.10.035 · Cited by 54 · see citing works
Foxo3a is essential for maintenance of the hematopoietic stem cell pool.
Miyamoto, K., Araki, K. Y., Naka, K., Arai, F., Takubo, K., Yamazaki, S., Matsuoka, S., Miyamoto, T., Ito, K., Ohmura, M., et al. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.02.001 · Cited by 41 · see citing works
p66Shc aging protein in control of fibroblasts cell fate
Suski, J. M., Karkucinska-Wieckowska, A., Lebiedzinska, M., Giorgi, C., Szczepanowska, J., Szabadkai, G., Duszynski, J., Pronicki, M., Pinton, P., & Wieckowski, M. R. (2011) · International Journal of Molecular Sciences · doi:10.3390/ijms12085373 · Cited by 22 · see citing works
Zhang, H., Pang, X., Yu, H., & Zhou, H. (2022) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.22939 · Cited by 18 · see citing works
- Authors
- Nemoto, S., & Finkel, T.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Finkel, Toren
- Venue
- Science
- Published
- 2002-03-29
- Volume
- 295
- Issue
- 5564
- Pages
- 2450-2452
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2023973783
- Cited by
- 818
- References
- 23
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 14 · 2023: 16 · 2022: 13 · 2021: 16 · 2020: 33 · 2019: 23 · 2018: 24 · 2017: 41 · 2016: 25 · 2015: 34 · 2014: 46 · 2013: 44 · 2012: 42
- FWCI
- 12.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Keywords
- p66Shc, forkhead transcription factor, FKHRL1, DAF-16, redox regulation, hydrogen peroxide, oxidative stress resistance, aging, longevity, Caenorhabditis elegans, hydrogen peroxide scavenging
- MeSH terms
- Forkhead Box Protein O1, Forkhead Box Protein O3, Src Homology 2 Domain-Containing, Transforming Protein 1, Acetylcysteine, Animals, Azoles, Blood, Cells, Cultured, Culture Media, DNA-Binding Proteins, Humans, Hydrogen Peroxide, Mutation, Nerve Tissue Proteins, Oxidation-Reduction, Phosphorylation, Proteins, Proto-Oncogene Proteins, Transcription Factors, Transfection, Signal Transduction, Free Radical Scavengers, Organoselenium Compounds, PC12 Cells, Protein Serine-Threonine Kinases, Reactive Oxygen Species, Oxidative Stress, Adaptor Proteins, Vesicular Transport, Adaptor Proteins, Signal Transducing, Proto-Oncogene Proteins c-akt, Mice, Rats, Forkhead Transcription Factors, Isoindoles, Shc Signaling Adaptor Proteins
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