The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
AMPK Facilitates Nuclear Accumulation of Nrf2 by Phosphorylating at Serine 550
Open accessAbstract
Nrf2 (nuclear factor erythroid 2-related factor 2) is an antioxidant transcription factor. AMP-activated protein kinase (AMPK) functions as a central regulator of cell survival in response to stressful stimuli. Nrf2 should be coordinated with the cell survival pathway controlled by AMPK, but so far the mechanistic connections remain undefined. This study investigated the role of AMPK in Nrf2 trafficking and its activity regulation. A subnetwork integrating neighbor molecules suggested direct interaction between AMPK and Nrf2. In cells, AMPK activation caused nuclear accumulation of Nrf2. In the in vitro kinase and peptide competition assays, AMPK phosphorylated Nrf2 at the Ser558 residue (Ser550 in mouse) located in the canonical nuclear export signal. Nrf2 with an S550A mutation failed to be accumulated in the nucleus after AMPK activation. Leptomycin B, a nuclear export inhibitor, did not enhance nuclear accumulation of wild-type Nrf2 (WT-Nrf2) activated by AMPK or a phospho-Ser550-mimetic Nrf2 mutant, corroborating the finding that AMPK facilitated nuclear accumulation of Nrf2, probably by inhibiting nuclear export. Activated glycogen synthase kinase 3β (GSK3β) diminished the basal nuclear level of Myc-S550A-Nrf2. Taking the data collectively, AMPK phosphorylates Nrf2 at the Ser550 residue, which, in conjunction with AMPK-mediated GSK3β inhibition, promotes nuclear accumulation of Nrf2 for antioxidant response element (ARE)-driven gene transactivation.
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Citations
Cites
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602
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AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway
Kensler, T. W., Wakabayashi, N., & Biswal, S. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.46.120604.141046 · Cited by 3,630
AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function
Hardie, D. G. (2011) · Genes & Development · doi:10.1101/gad.17420111 · Cited by 1,638
Rada, P., Rojo, A. I., Chowdhry, S., McMahon, M., Hayes, J. D., & Cuadrado, A. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.01204-10 · Cited by 759 · cited 1×
“In another study, GSK3 phosphorylated Nrf2 at several serine residues (51).”
BackgroundKukidome, D., Nishikawa, T., Sonoda, K., Imoto, K., Fujisawa, K., Yano, M., Motoshima, H., Taguchi, T., Matsumura, T., & Araki, E. (2006) · Diabetes · doi:10.2337/diabetes.55.01.06.db05-0943 · Cited by 504
Exposure to hydrogen peroxide induces oxidation and activation of AMP-activated protein kinase
Zmijewski, J. W., Banerjee, S., Bae, H., Friggeri, A., Lazarowski, E. R., & Abraham, E. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.143685 · Cited by 441
Cited by
The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging
Yu, C., & Xiao, J.-H. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6635460 · Cited by 537
NRF2 as a Therapeutic Target in Neurodegenerative Diseases
Brandes, M. S., & Gray, N. E. (2020) · ASN Neuro · doi:10.1177/1759091419899782 · Cited by 297
Cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents
Wang, Z., Chen, Z., Jiang, Z., Luo, P., Liu, L., Huang, Y., Wang, H., Wang, Y., Long, L., Tan, X., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10386-8 · Cited by 219
Tanaka, M., Kishimoto, Y., Sasaki, M., Sato, A., Kamiya, T., Kondo, K., & Iida, K. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/9364364 · Cited by 154
Natural Nrf2 Modulators for Skin Protection
Boo, Y. C. (2020) · Antioxidants · doi:10.3390/antiox9090812 · Cited by 69
Metadata
- Authors
- Joo, M. S., Kim, W. D., Lee, K. Y., Kim, J. H., Koo, J. H., & Kim, S. G.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2016-07-01
- Volume
- 36
- Issue
- 14
- Pages
- 1931-1942
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2346475789
- Cited by
- 500
- References
- 8
- FWCI
- 16.70
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: AMPK Facilitates Nuclear Accumulation of Nrf2 by Phosphorylating at Serine 550. https://app.cochat.ai/papers/10.1128/mcb.00118-16
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- Joo, M. S., Kim, W. D., Lee, K. Y., Kim, J. H., Koo, J. H., & Kim, S. G. (2016). AMPK Facilitates Nuclear Accumulation of Nrf2 by Phosphorylating at Serine 550. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.00118-16
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