CoChat
Sign Up
Cited by 660

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Keap1/Nrf2 Signaling Regulates Oxidative Stress Tolerance and Lifespan in Drosophila

Sykiotis, Gerasimos P., Bohmann, Dirk·2008·Developmental Cell
DOI 10.1016/j.devcel.2007.12.002
Open this paper in CoChat — free account

Abstract

Keap1/Nrf2 signaling defends organisms against the detrimental effects of oxidative stress and has been suggested to abate its consequences, including aging-associated diseases like neurodegeneration, chronic inflammation, and cancer. Nrf2 is a prominent target for drug discovery, and Nrf2-activating agents are in clinical trials for cancer chemoprevention. However, aberrant activation of Nrf2 by keap1 somatic mutations may contribute to carcinogenesis and promote resistance to chemotherapy. To evaluate potential functions of Keap1 and Nrf2 for organismal homeostasis, we characterized the pathway in Drosophila. We demonstrate that Keap1/Nrf2 signaling in the fruit fly is activated by oxidants, induces antioxidant and detoxification responses, and confers increased tolerance to oxidative stress. Importantly, keap1 loss-of-function mutations extend the lifespan of Drosophila males, supporting a role for Nrf2 signaling in the regulation of longevity. Interestingly, cancer chemopreventive drugs potently stimulate Drosophila Nrf2 activity, suggesting the fruit fly as an experimental system to identify and characterize such agents.

Overview

Integrity signals

Registry

Crossref · 10.1016/j.devcel.2007.12.002

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 42

  1. An, 2003, SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response, Genes Dev., 17, 1882, 10.1101/gad.1107803 · DOI
  2. Barolo, 2000, GFP and β-galactosidase transformation vectors for promoter/enhancer analysis in Drosophila, Biotechniques, 29, 10.2144/00294bm10 · DOI
  3. Bauer, 2005, Neuronal expression of p53 dominant-negative proteins in adult Drosophila melanogaster extends life span, Curr. Biol., 15, 2063, 10.1016/j.cub.2005.10.051 · DOI
  4. Bilen, 2005, Drosophila as a model for human neurodegenerative disease, Annu. Rev. Genet., 39, 153, 10.1146/annurev.genet.39.110304.095804 · DOI
  5. Blackwell, 1994, Formation of a monomeric DNA binding domain by Skn-1 bZIP and homeodomain elements, Science, 266, 621, 10.1126/science.7939715 · DOI
  6. Brand, 1993, Targeted gene expression as a means of altering cell fates and generating dominant phenotypes, Development, 118, 401, 10.1242/dev.118.2.401 · DOI
  7. Chan, 1996, NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development, Proc. Natl. Acad. Sci. USA, 93, 13943, 10.1073/pnas.93.24.13943 · DOI
  8. Clancy, 2001, Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein, Science, 292, 104, 10.1126/science.1057991 · DOI
  9. Dugan, 2005, Reactive oxygen species and aging: evolving questions, Sci. Aging Knowledge Environ., 2005, pe20, 10.1126/sageke.2005.26.pe20 · DOI
  10. Giot, 2003, A protein interaction map of Drosophila melanogaster, Science, 302, 1727, 10.1126/science.1090289 · DOI · Paper page
  11. Glintborg, 2006, Oltipraz chemoprevention trial in Qidong, People's Republic of China: unaltered oxidative biomarkers, Free Radic. Biol. Med., 41, 1010, 10.1016/j.freeradbiomed.2006.06.015 · DOI
  12. Harman, 1956, Aging: a theory based on free radical and radiation chemistry, J. Gerontol., 11, 298, 10.1093/geronj/11.3.298 · DOI · Paper page
  13. Inoue, 2005, The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response, Genes Dev., 19, 2278, 10.1101/gad.1324805 · DOI
  14. Itoh, 2004, Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles, Free Radic. Biol. Med., 36, 1208, 10.1016/j.freeradbiomed.2004.02.075 · DOI
  15. Jaiswal, 2004, Regulation of antioxidant response element-dependent induction of detoxifying enzyme synthesis, Methods Enzymol., 378, 221, 10.1016/S0076-6879(04)78018-0 · DOI
  16. Jasper, 2001, The genomic response of the Drosophila embryo to JNK signaling, Dev. Cell, 1, 579, 10.1016/S1534-5807(01)00045-4 · DOI
  17. Kensler, 1999, Development of cancer chemopreventive agents: oltipraz as a paradigm, Chem. Res. Toxicol., 12, 113, 10.1021/tx980185b · DOI
  18. Kobayashi, 2002, Identification of the interactive interface and phylogenic conservation of the Nrf2-Keap1 system, Genes Cells, 7, 807, 10.1046/j.1365-2443.2002.00561.x · DOI
  19. Lee, 2007, An auto-regulatory loop between stress sensors INrf2 and Nrf2 controls their cellular abundance, J. Biol. Chem., 282, 36412, 10.1074/jbc.M706517200 · DOI
  20. Lee, 2003, Making a better RNAi vector for Drosophila: use of intron spacers, Methods, 30, 322, 10.1016/S1046-2023(03)00051-3 · DOI
  21. McGinnis, 1998, A cap 'n' collar protein isoform contains a selective Hox repressor function, Development, 125, 4553, 10.1242/dev.125.22.4553 · DOI
  22. McGuire, 2004, Spatiotemporal gene expression targeting with the TARGET and gene-switch systems in Drosophila, Sci. STKE, 2004, pl6, 10.1126/stke.2202004pl6 · DOI
  23. Nioi, 2003, Identification of a novel Nrf2-regulated antioxidant response element (ARE) in the mouse NAD(P)H:quinone oxidoreductase 1 gene: reassessment of the ARE consensus sequence, Biochem. J., 374, 337, 10.1042/bj20030754 · DOI
  24. Orr, 2005, Overexpression of glutamate-cysteine ligase extends life span in Drosophila melanogaster, J. Biol. Chem., 280, 37331, 10.1074/jbc.M508272200 · DOI
  25. Prestera, 1993, The electrophile counterattack response: protection against neoplasia and toxicity, Adv. Enzyme Regul., 33, 281, 10.1016/0065-2571(93)90024-8 · DOI
  26. Sawicki, 2003, Cloning, expression and biochemical characterization of one Epsilon-class (GST-3) and ten Delta-class (GST-1) glutathione S-transferases from Drosophila melanogaster, and identification of additional nine members of the Epsilon class, Biochem. J., 370, 661, 10.1042/bj20021287 · DOI
  27. Singh, 2006, Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer, PLoS Med., 3, e420, 10.1371/journal.pmed.0030420 · DOI · Paper page
  28. Sohal, 2002, Mechanisms of aging: an appraisal of the oxidative stress hypothesis, Free Radic. Biol. Med., 33, 575, 10.1016/S0891-5849(02)00886-9 · DOI
  29. Sporn, 2005, Cancer chemoprevention: scientific promise, clinical uncertainty, Nat. Clin. Pract. Oncol., 2, 518, 10.1038/ncponc0319 · DOI
  30. Su, 1998, X-gal staining of Drosophila embryos compatible with antibody staining or in situ hybridization, Biotechniques, 24, 918, 10.2144/98246bm03 · DOI
  31. Suh, 2004, Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid, Proc. Natl. Acad. Sci. USA, 101, 3381, 10.1073/pnas.0400282101 · DOI
  32. Takagi, 2004, MafT, a new member of the small Maf protein family in zebrafish, Biochem. Biophys. Res. Commun., 320, 62, 10.1016/j.bbrc.2004.05.131 · DOI
  33. Tu, 2002, The demography of slow aging in male and female Drosophila mutant for the insulin-receptor substrate homologue chico, Aging Cell, 1, 75, 10.1046/j.1474-9728.2002.00010.x · DOI
  34. van Muiswinkel, 2005, The Nrf2-ARE signalling pathway: promising drug target to combat oxidative stress in neurodegenerative disorders, Curr. Drug Targets CNS Neurol. Disord., 4, 267, 10.2174/1568007054038238 · DOI
  35. Veraksa, 2000, Cap 'n' collar B cooperates with a small Maf subunit to specify pharyngeal development and suppress deformed homeotic function in the Drosophila head, Development, 127, 4023, 10.1242/dev.127.18.4023 · DOI
  36. Wakabayashi, 2003, Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation, Nat. Genet., 35, 238, 10.1038/ng1248 · DOI
  37. Wang, 2003, JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila, Dev. Cell, 5, 811, 10.1016/S1534-5807(03)00323-X · DOI
  38. Wang, 2005, JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling, Cell, 121, 115, 10.1016/j.cell.2005.02.030 · DOI
  39. Wu, 2006, A protocol for mosaic analysis with a repressible cell marker (MARCM) in Drosophila, Nat. Protoc., 1, 2583, 10.1038/nprot.2006.320 · DOI
  40. Yu, 2005, Nrf2 as a target for cancer chemoprevention, Mutat. Res., 591, 93, 10.1016/j.mrfmmm.2005.04.017 · DOI
  41. Zhang, 2006, Mechanistic studies of the Nrf2-Keap1 signaling pathway, Drug Metab. Rev., 38, 769, 10.1080/03602530600971974 · DOI
  42. Zhang, 1997, Oltipraz chemoprevention trial in Qidong, Jiangsu Province, People's Republic of China, J. Cell. Biochem. Suppl., 28–29, 166, 10.1002/(SICI)1097-4644(1997)28/29+<166::AID-JCB20>3.0.CO;2-E · DOI

Cited by

Sorted by citations

Metadata

Authors
Sykiotis, G. P., & Bohmann, D.
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2008-01
Volume
14
Issue
1
Pages
76-85
ISSN
1534-5807
DOI
10.1016/j.devcel.2007.12.002
Cited by
660
References
5
Language
en
Licence

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