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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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“The nuclear factor-kappaB (NF-kB) transcription factor family is composed of five structurally related members that possess an N-terminal Rel homology (RH) domain involved in protein– protein interactions and DNA binding (Ghosh and Karin, 2002).”
NF-κB activation by double-strand breaks
Habraken, Y., & Piette, J. G. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.07.015 · Cited by 144
RETRACTED: Kinase inhibitors and airway inflammation
Adcock, I. M., Chung, K. F., Caramori, G., & Ito, K. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.12.054 · Cited by 141
RetractedNF-κB as potential target in the treatment of melanoma
Madonna, G., Ullmann, C. D., Gentilcore, G., Palmieri, G., & Ascierto, P. A. (2012) · Journal of Translational Medicine · doi:10.1186/1479-5876-10-53 · Cited by 139
“Their activation is the result of a variety of different stimuli, including those activating some membrane receptors [B cell receptor (BCR), tumor necrosis factor receptors (TNFR)] and several extracellular stimuli (inflammatory cytokines, viral and bacterial infections, oxidative and DNA-damaging agents, UV light and…”
BackgroundMetastasis suppressor, NDRG1, mediates its activity through signaling pathways and molecular motors
Sun, J., Zhang, D., Bae, D.-H., Sahni, S., Jansson, P. J., Zheng, Y., Zhao, Q., Yue, F., Zheng, M., Kovačević, Ž., et al. (2013) · Carcinogenesis · doi:10.1093/carcin/bgt163 · Cited by 140
Characterization of NF-κΒ/IκΒ Proteins in Zebra Fish and Their Involvement in Notochord Development
Correa, R. G., Tergaonkar, V., Ng, J. K., Dubova, I., Izpisúa‐Belmonte, J. C., & Verma, I. M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.12.5257-5268.2004 · Cited by 140
“The NF- signaling pathway plays a crucial role in physiological events such as inflammation, immune response, apoptosis, cell growth, and differentiation ( 9 , 18, 24, 43).”
BackgroundStrassheim, D., Asehnoune, K., Park, J.-S., Kim, J. Y., He, Q., Richter, D., Kuhn, K., Mitra, S., & Abraham, E. H. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.9.5727 · Cited by 141
OsteoimmunologyPreprint
Okamoto, K., & Takayanagi, H. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031245 · Cited by 146
“The NF-κB family of transcription factors has five members: p50 (processed from p105), p52 (processed from p100), RelA (p65), RelB, and c-Rel (Ghosh and Karin 2002; Hayden and Ghosh 2008).”
Bu, D.-X., Hemdahl, A.-L., Gabrielsen, A., Fuxe, J., Zhu, C., Eriksson, P. O., & Yan, Z.-Q. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.050706 · Cited by 138
“Activation of NF- B is a pivotal mechanism underlying the induction of genes implicated in vascular inflammation, cell proliferation, and death.(18) Our recent study demonstrated that in contrast to the resolved NF- B activation in the media, the intima exhibited a persistent NF- B activation coupled with high levels…”
Basak, S., Shih, V. F.-S., & Hoffmann, A. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01469-07 · Cited by 138
Long non-coding RNAs and nuclear factor-κB crosstalk in cancer and other human diseases
Gupta, S. C., Awasthee, N., Rai, V., Chava, S. P., Gunda, V., & Challagundla, K. B. (2019) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2019.188316 · Cited by 138
Tpl2/Cot Signals Activate ERK, JNK, and NF-κB in a Cell-type and Stimulus-specific Manner
Das, S., Cho, J., Lambertz, I., Kelliher, M. A., Eliopoulos, A. G., Du, K., & Tsichlis, P. N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412837200 · Cited by 138
Histone deacetylase inhibitors: insights into mechanisms of lethality
Rosato, R. R., & Grant, S. (2005) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.9.4.809 · Cited by 138
“The cycle ends with newly synthesised IκBα entering the nucleus, displacing NF-κB from its DNA-binding sites, and transporting it back to the cytoplasm where it is inactive [118,126].”
TRAF Family Proteins Link PKR with NF-κB Activation
Gil, J., García, M. Á., Gómez‐Puertas, P., Guerra, S., Rullás, J., Nakano, H., Alcamı́, J., & Estéban, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.10.4502-4512.2004 · Cited by 138
Schmeißer, M. J., Baumann, B., Johannsen, S., Vindedal, G. F., Jensen, V., Hvalby, Ø., Sprengel, R., Seither, J., Maqbool, A., Magnutzki, A., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0111-12.2012 · Cited by 137
“Upon activation, the I B kinase (IKK) complex composed of IKK1 (IKK ), IKK2 (IKK ), and NEMO (IKK ), phosphorylates I B proteins, thereby initiating their proteasomal degradation followed by the release and nuclear translocation of active NF- B complexes (Ghosh and Karin, 2002; Scheidereit, 2006).”
Regulation of innate immunity by NADPH oxidase
Segal, B. H., Grimm, M. J., Khan, A. N. H., Han, W., & Blackwell, T. S. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.04.022 · Cited by 140
“The prototypical NF-kB complex is the RelA (p65)/p50 heterodimer, which resides in cytoplasm by forming complexes with inhibitory kB (IkB) under unstimulated conditions [58].”
Shetty, S., Graham, B. A., Brown, J. G., Hu, X., Vegh-Yarema, N., Harding, G. A., Paul, J. T., & Gibson, S. B. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.13.5404-5416.2005 · Cited by 136
“NF-B is involved in both cell survval and apoptosis (4, 9 , 15).”
BackgroundDubé, N., & Tremblay, M. L. (2005) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2005.07.030 · Cited by 138
Santilli, G., Aronow, B. J., & Sala, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c300252200 · Cited by 138
Giri, S., Rattan, R., Singh, A. K., & Singh, I. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.8.5196 · Cited by 136
Stabilization of p53 Is a Novel Mechanism for Proapoptotic Function of NF-κB
Fujioka, S., Schmidt, C., Sclabas, G. M., Li, Z., Pelicano, H., Peng, B., Yao, A., Niu, J., Zhang, W., Evans, D. B., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313435200 · Cited by 139
Hijacking of Host Cell IKK Signalosomes by the Transforming Parasite Theileria
Heussler, V. T., Rottenberg, S., Schwab, R., Küenzi, P., Fernandez, P. C., McKellar, S., Shiels, B. R., Chen, Z. J., Orth, K., Wallach, D., et al. (2002) · Science · doi:10.1126/science.1075462 · Cited by 137
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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