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Missing Pieces in the NF-κB Puzzle
Open accessAbstract
The regulation of the transcription factor NF-kappaB activity occurs at several levels including controlled cytoplasmic-nuclear shuttling and modulation of its transcriptional activity. A critical component in NF-kappaB regulation is the IkappaB kinase (IKK) complex. This review is focused on recent progress as well as unanswered questions regarding the regulation and function of NF-kappaB and IKK.
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“In the NF-κB system (e.g. [2020-2024]) (Fig 8), NF-κB is normally held inactive in the cytoplasm by binding to an inhibitor IκB (often IκBα). Pro-inflammatory cytokines such as TNF-α, LPS [2025-2030] and IL-1 [2031] act by binding to receptors at the cell surface and initiating signalling pathways that lead to the activation of a particular kinase, IκB kinase or IKK. This kinase phosphorylates the”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [2020]
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Curcumin blocks NF-κB and the motogenic response in Helicobacter pylori-infected epithelial cells
Foryst‐Ludwig, A., Neumann, M., Schneider‐Brachert, W., & Naumann, M. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.02.158 · Cited by 108
Molecular targets of [6]‐gingerol: Its potential roles in cancer chemoprevention
Oyagbemi, A. A., Saba, A. B., & Azeez, O. I. (2010) · BioFactors · doi:10.1002/biof.78 · Cited by 108
Immunosuppressive properties of flavonoids isolated from Boerhaavia diffusa Linn.
Pandey, R., Maurya, R., Singh, G., Sathiamoorthy, B., & Naik, S. (2004) · International Immunopharmacology · doi:10.1016/j.intimp.2004.11.001 · Cited by 108
Estrogen, NFκB, and the Heat Shock Response
Stice, J. P., & Knowlton, A. A. (2008) · Molecular Medicine · doi:10.2119/2008-00026.stice · Cited by 109
Out of Control: The Role of the Ubiquitin Proteasome System in Skeletal Muscle during Inflammation
Haberecht-Müller, S., Krüger, E., & Fielitz, J. (2021) · Biomolecules · doi:10.3390/biom11091327 · Cited by 108
Turrin, N. P., & Rivest, S. (2004) · Experimental Biology and Medicine · doi:10.1177/153537020422901003 · Cited by 107
Morelli, M. B., Offidani, M., Alesiani, F., Discepoli, G., Liberati, S., Olivieri, A., Santoni, M., Santoni, G., Leoni, P., & Nabissi, M. (2013) · International Journal of Cancer · doi:10.1002/ijc.28591 · Cited by 112
IKK-2 is required for TNF-α-induced invasion and proliferation of human mesenchymal stem cells
Böcker, W., Docheva, D., Prall, W. C., Egea, V., Pappou, E. P., Roßmann, O., Popov, C., Mutschler, W., Ries, C., & Schieker, M. (2008) · Journal of Molecular Medicine · doi:10.1007/s00109-008-0378-3 · Cited by 108
Damiano, S., Muscariello, E., Rosa, G. L., Maro, M. D., Mondola, P., & Santillo, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20153815 · Cited by 116
Brinkmann, M. M., & Schulz, T. F. (2006) · Journal of General Virology · doi:10.1099/vir.0.81598-0 · Cited by 107
“Both the canonical (reviewed by Ghosh & Karin, 2002) and the non-canonical (reviewed by Pomerantz & Baltimore, 2002) NF-kB pathways can be activated by LMP1.”
BackgroundGuzmán, M. L., Li, X., Corbett, C. A., Rossi, R. M., Bushnell, T. P., Liesveld, J. L., Hébert, J., Young, F. M., & Jordan, C. T. (2007) · Blood · doi:10.1182/blood-2007-05-088815 · Cited by 106
Kim, R., Emi, M., & Tanabe, K. (2005) · Cancer Biology & Therapy · doi:10.4161/cbt.4.9.2101 · Cited by 110
Mikenberg, I., Widera, D., Kaus, A., Kaltschmidt, B., & Kaltschmidt, C. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000589 · Cited by 107
Amici, C., Rossi, A., Costanzo, A., Ciafrè, S., Marinari, B., Balsamo, M., Levrero, M., & Santoro, M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512366200 · Cited by 107
Choi, M., Rolle, S., Wellner, M., Cardoso, M. C., Scheidereit, C., Luft, F. C., & Kettritz, R. (2003) · Blood · doi:10.1182/blood-2002-09-2960 · Cited by 107
Bacterial Colonization, Probiotics, and Necrotizing Enterocolitis
Claud, E. C., & Walker, W. A. (2008) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e31815a57a8 · Cited by 106
“In its resting state, NF-kB dimers are bound in the cytoplasm to inhibitory kB (IkB) proteins.(27) Cell stimulation can trigger signaling pathways leading to the activation of IkB kinase (IKK), which then phosphorylates IkB, targeting it for ubiquitination and degradation by the 26S proteasome.”
Role of Caspase-1 in the Pathogenesis of Inflammatory-Associated Chronic Noncommunicable Diseases
Molla, M. D., Akalu, Y., Geto, Z., Dagnew, B., Ayelign, B., & Shibabaw, T. (2020) · Journal of Inflammation Research · doi:10.2147/jir.s277457 · Cited by 119
Emerging anti-inflammatory strategies for COPD
Cazzola, M., Page, C. P., Calzetta, L., & Matera, M. G. (2012) · European Respiratory Journal · doi:10.1183/09031936.00213711 · Cited by 107
Aldosterone Activates NF-κB in the Collecting Duct
Leroy, V. A. A., de Seigneux, S., Agassiz, V., Hasler, U., Rafestin-Oblin, M. E., Vinciguerra, M., Martin, P., & Féraille, E. (2008) · Journal of the American Society of Nephrology · doi:10.1681/asn.2008020232 · Cited by 114
Denkers, E., Butcher, B. A., Rı́o, L. D., & Kim, L. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.00180.x · Cited by 105
Deciphering the pathway from the TCR to NF-κB
Weil, R., & Israël, A. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401856 · Cited by 105
“Recently, a second NF-kB activation pathway (called the alternative pathway) based on regulated processing of NF-kB2/p100 precursor protein has been identified.(2,3) This pathway is involved in NF-kB activation in response to a specific set of stimuli that includes BAFF, LTb”
Metadata
- Authors
- Ghosh, S., & Karin, M.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California San Diego (US)
- Corresponding author
- Ghosh, Sankar
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2002-04
- Volume
- 109
- Issue
- 2
- Pages
- S81-S96
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1976382352
- Cited by
- 3,638
- References
- 158
- Citations by year
- 2026: 29 · 2025: 65 · 2024: 66 · 2023: 49 · 2022: 66 · 2021: 94 · 2020: 100 · 2019: 84 · 2018: 103 · 2017: 111 · 2016: 122 · 2015: 141 · 2014: 134 · 2013: 144 · 2012: 189
- FWCI
- 19.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- NF-κB, IκB kinase complex, transcription factor regulation, transcriptional activity, IκB, signal transduction
- MeSH terms
- Animals, Cell Nucleus, Cytoplasm, Enzyme Activation, Gene Expression Regulation, Humans, Signal Transduction, NF-kappa B, Protein Serine-Threonine Kinases, Catalytic Domain, Active Transport, Cell Nucleus, I-kappa B Kinase
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