The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
The transcription factor NF‐E2‐related Factor 2 (Nrf2): a protooncogene?
Open accessAbstract
The transcription factor Nrf2 is responsible for regulating a battery of antioxidant and cellular protective genes, primarily in response to oxidative stress. A member of the cap ‘n’ collar family of transcription factors, Nrf2 activation is tightly controlled by a series of signaling events. These events can be separated into the basal state, a preinduction response, gene induction, and finally a postinduction response, culminating in the restoration of redox homeostasis. However, despite the immensely intricate level of control the cellular environment imposes on Nrf2 activity, there are many opportunities for perturbations to arise in the signaling events that favor carcinogenesis and, therefore, implicate Nrf2 as both a tumor suppressor and a protooncogene. Herein, we highlight the ways in which Nrf2 is regulated, and discuss some of the Nrf2‐inducible antioxidant (NQO1, NQO2, HO‐1, GCLC), antiapoptotic (Bcl‐2), metabolic (G6PD, TKT, PPARγ), and drug efflux transporter (ABCG2, MRP3, MRP4) genes. In addition, we focus on how Nrf2 functions as a tumor suppressor under normal conditions and how its ability to detoxify the cellular environment makes it an attractive target for other oncogenes either via stabilization or degradation of the transcription factor. Finally, we discuss some of the ways in which Nrf2 is being considered as a therapeutic target for cancer treatment.—Shelton, P., Jaiswal, A. K. The transcription factor NF‐E2‐related factor 2 (Nrf2): a protooncogene? FASEB J. 27, 414–423 (2013). www.fasebj.org
Overview
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
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., et al. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6943 · Cited by 3,999
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
DeNicola, G. M., Karreth, F. A., Humpton, T. J., Gopinathan, A., Wei, C., Frese, K., Mangal, D., Yu, K. H., Yeo, C. J., Calhoun, E. S., et al. (2011) · Nature · doi:10.1038/nature10189 · Cited by 2,277
Serine/threonine phosphatases: mechanism through structure
Shi, Y. (2009) · Cell · doi:10.1016/j.cell.2009.10.006 · Cited by 1,488
Zhang, D. D., & Hannink, M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.22.8137-8151.2003 · Cited by 1,480 · cited 1×
“The inhibition of Nrf2 is principally achieved by INrf2 (Keap1), which is an adaptor protein that facilitates ubiquitination and degradation of Nrf2 (8, 41, 42).”
BackgroundMolecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution
Taguchi, K., Motohashi, H., & Yamamoto, M. (2011) · Genes to Cells · doi:10.1111/j.1365-2443.2010.01473.x · Cited by 1,478
Nrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming
Mitsuishi, Y., Taguchi, K., Kawatani, Y., Shibata, T., Nukiwa, T., Aburatani, H., Yamamoto, M., & Motohashi, H. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.05.016 · Cited by 1,395 · cited 1×
“More recently, a seminal paper highlighted the ability of Nrf2 to regulate many of the enzymes responsible for reprogramming energy metabolism and de novo nucleotide synthesis, such as glucose6-phosphate dehydrogenase (G6PD) and transketolase (TKT), and that these enzymes are required to regulate tumor growth (40).”
BackgroundDNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA
STEHELIN, D., VARMUS, H. E., BISHOP, J. M., & VOGT, P. K. (1976) · Nature · doi:10.1038/260170a0 · Cited by 1,321 · cited 1×
“First described by Varmus, Bishop, and colleagues (95) in 1976 with c-Src, a protooncogene is a normal gene that typically controls cell growth and division, but when it obtains a gain of function mutation, or its expression is altered, it becomes oncogenic (95, 96).”
BackgroundNRF2 and cancer: the good, the bad and the importance of context
Sporn, M. B., & Liby, K. T. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3278 · Cited by 1,067 · cited 3×
“role is dependent on the stage of tumorigenesis (66).”
BackgroundInfluentialDysfunctional KEAP1–NRF2 Interaction in Non-Small-Cell Lung Cancer
Singh, A., Misra, V., Thimmulappa, R. K., Lee, H., Ames, S., Hoque, M. O., Herman, J. G., Baylin, S. B., Sidransky, D., Gabrielson, E., et al. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030420 · Cited by 1,060
Stress-activated cap’n’collar transcription factors in aging and human disease
Sykiotis, G. P., & Bohmann, D. (2010) · Science Signaling · doi:10.1126/scisignal.3112re3 · Cited by 776 · cited 3×
“At the center of this theory is the notion that aging is the result of progressive oxidative damage to cells that is caused by free radicals (17).”
BackgroundInfluential
Cited by
Niture, S. K., Khatri, R., & Jaiswal, A. K. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.02.008 · Cited by 868
Self-citationParadoxical Roles of Antioxidant Enzymes: Basic Mechanisms and Health Implications
Lei, X. G., Zhu, J.-H., Cheng, W.-H., Bao, Y., Ho, Y.-S., Reddi, A. R., Holmgren, A., & Arnér, E. S. J. (2016) · Physiological Reviews · doi:10.1152/physrev.00010.2014 · Cited by 429
Gào, X., & Schöttker, B. (2017) · Oncotarget · doi:10.18632/oncotarget.17128 · Cited by 147
Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance
Saddawi-Konefka, R., Seelige, R., Gross, E. T. E., Levy, E., Searles, S. C., Washington, A., Santosa, E. K., Liu, B., O’Sullivan, T. E., Harismendy, O., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.07.075 · Cited by 126
Huang, K.-F., Ma, K.-H., Jhap, T.-Y., Liu, P.-S., & Chueh, S.-H. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.06.020 · Cited by 27
Metadata
- Authors
- Shelton, P., & Jaiswal, A. K.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2012-10-29
- Volume
- 27
- Issue
- 2
- Pages
- 414-423
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2119511051
- Cited by
- 186
- References
- 19
- FWCI
- 8.13
- Type
- journal article
- Language
- en
- Open access
- green
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: The transcription factor NF‐E2‐related Factor 2 (Nrf2): a protooncogene? https://app.cochat.ai/papers/10.1096/fj.12-217257
- The paper
- Shelton, P., & Jaiswal, A. K. (2013). The transcription factor NF‐E2‐related Factor 2 (Nrf2): a protooncogene? The FASEB Journal. https://doi.org/10.1096/fj.12-217257
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
