Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway
Open accessAbstract
The diverse cellular and biological functions of the nuclear factor kappa B (NF-kappaB) pathway, together with the catastrophic consequences of its aberrant regulation, demand specific and highly regulated control of its activity. As described in this review, regulation of the NF-kappaB pathway is brought about through multiple post-translational modifications that control the activity of the core components of NF-kappaB signaling: the IkappaB kinase (IKK) complex, the IkappaB proteins and the NF-kappaB subunits themselves. These regulatory modifications, which include phosphorylation, ubiquitination, acetylation, sumoylation and nitrosylation, can vary, depending on the nature of the NF-kappaB-inducing stimulus. Moreover, they frequently have distinct, sometimes antagonistic, functional consequences and the same modification can have different effects depending on the context. Given the important role of NF-kappaB in human health and disease, understanding these pathways will not only provide valuable insights into mechanism and function, but could also lead to new drug targets and the development of diagnostic and prognostic biomarkers for many pathological conditions.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Modifications of p65 after translation, including phosphorylation and acetylation, change its activity by affecting DNA binding, its interaction with nuclear IκBα, and its association with chromatin modifiers like HAT and HDAC.
“Although NF-κB nuclear translocation is the best-known mechanism for its activation [12], several lines of evidence indicate that posttranslational modifications in p65 subunit, such as phosphorylation and acetylation, impact its activity by altering DNA binding, interaction with inhibitor of κB α (IκBα) in the nucleus, and association with chromatin structure modifiers such as histone acetyltrans”
From Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes (2013) · cites this paper as [32]
Cites
Hayden, M. S., & Ghosh, S. (2004) · Genes & Development · doi:10.1101/gad.1228704 · Cited by 3,842 · see citing works
Activators and target genes of Rel/NF-κB transcription factors
Pahl, H. L. (1999) · Oncogene · doi:10.1038/sj.onc.1203239 · Cited by 3,727 · see citing works
Activators and Target Genes of Rel/NF-кB Transcription Factors
Loop, T., & Pahl, H. L. (2003) · Springer eBooks · doi:10.1007/978-94-010-0163-2_1 · Cited by 3,179 · see citing works
Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase
Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A., & Mayo, M. W. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600244 · Cited by 2,750 · see citing works
The two NF-κB activation pathways and their role in innate and adaptive immunity
Bonizzi, G., & Karin, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.03.008 · Cited by 2,535 · see citing works
Introduction to NF-κB: players, pathways, perspectives
Gilmore, T. D. (2006) · Oncogene · doi:10.1038/sj.onc.1209954 · Cited by 2,227 · see citing works
NF-κB activation by tumour necrosis factor requires the Akt serine–threonine kinase
Özeş, O. N., Mayo, L. D., Gustin, J. A., Pfeffer, S. R., Pfeffer, L. M., & Donner, D. B. (1999) · Nature · doi:10.1038/43466 · Cited by 2,175 · see citing works
TAK1 is a ubiquitin-dependent kinase of MKK and IKK
Wang, C., Deng, L., Hong, M., Akkaraju, G. R., Inoue, J.-I., & Chen, Z. J. (2001) · Nature · doi:10.1038/35085597 · Cited by 2,125 · see citing works
IKK-1 and IKK-2: Cytokine-Activated IκB Kinases Essential for NF-κB Activation
Mercurio, F., Zhu, H., Murray, B. W., Shevchenko, A., Bennett, B. L., Li, J. W., Young, D. B., Barbosa, M. S., Mann, M., Manning, A. M., et al. (1997) · Science · doi:10.1126/science.278.5339.860 · Cited by 2,042 · see citing works
Zandi, E., Rothwarf, D. M., Delhase, M., Hayakawa, M., & Karin, M. (1997) · Cell · doi:10.1016/s0092-8674(00)80406-7 · Cited by 1,814 · see citing works
Phosphorylation of NF-κB and IκB proteins: implications in cancer and inflammation
Viatour, P., Merville, M., Bours, V., & Chariot, A. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.11.009 · Cited by 1,497 · see citing works
Activation by IKKα of a Second, Evolutionary Conserved, NF-κB Signaling Pathway
Senftleben, U., Cao, Y., Xiao, G., Greten, F. R., Krähn, G. M., Bonizzi, G., Chen, Y., Hu, Y., Fong, A., Sun, S., et al. (2001) · Science · doi:10.1126/science.1062677 · Cited by 1,361 · see citing works
Shaping the nuclear action of NF-κB
Chen, L., & Greene, W. C. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1368 · Cited by 1,219 · see citing works
Zhong, H., Voll, R. E., & Ghosh, S. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80066-0 · Cited by 1,210 · see citing works
Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression
Nelson, D. E., Ihekwaba, A. E. C., Elliott, M., Johnson, J. R., Gibney, C. A., Foreman, B. E., Nelson, G., See, V., Horton, C. A., Spiller, D. G., et al. (2004) · Science · doi:10.1126/science.1099962 · Cited by 1,186 · see citing works
Ubiquitin signalling in the NF-κB pathway
Chen, Z. J. (2005) · Nature Cell Biology · doi:10.1038/ncb0805-758 · Cited by 1,184 · see citing works
IκB Kinase-β: NF-κB Activation and Complex Formation with IκB Kinase-α and NIK
Woronicz, J. D., Gao, X., Cao, Z., Rothe, M., & Goeddel, D. V. (1997) · Science · doi:10.1126/science.278.5339.866 · Cited by 1,183 · see citing works
SUMO-1 Modification of IκBα Inhibits NF-κB Activation
Desterro, J. M. P., Rodríguez, M. S., & Hay, R. T. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80133-1 · Cited by 1,048 · see citing works
15-Deoxy-Δ 12,14 -prostaglandin J 2 inhibits multiple steps in the NF-κB signaling pathway
Straus, D. S., Pascual, G., Li, M., Welch, J. S., Ricote, M., Hsiang, C., Sengchanthalangsy, L. L., Ghosh, G., & Glass, C. K. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.9.4844 · Cited by 1,004 · see citing works
Ea, C.-K., Deng, L., Xia, Z.-P., Pineda, G., & Chen, Z. J. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.026 · Cited by 998 · see citing works
The Phosphorylation Status of Nuclear NF-ΚB Determines Its Association with CBP/p300 or HDAC-1
Zhong, H., May, M. J., Jimi, E., & Ghosh, S. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00477-x · Cited by 930 · see citing works
Positive and Negative Regulation of IκB Kinase Activity Through IKKβ Subunit Phosphorylation
Delhase, M., Hayakawa, M., Chen, Y., & Karin, M. (1999) · Science · doi:10.1126/science.284.5412.309 · Cited by 852 · see citing works
NF-κB-Inducing Kinase Regulates the Processing of NF-κB2 p100
Xiao, G., Harhaj, E. W., & Sun, S. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00187-3 · Cited by 836 · see citing works
Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF‐κB
Chen, L., Mu, Y., & Greene, W. C. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf660 · Cited by 827 · see citing works
IκB Kinases Phosphorylate NF-κB p65 Subunit on Serine 536 in the Transactivation Domain
Sakurai, H., Chiba, H., Miyoshi, H., Sugita, T., & Toriumi, W. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.43.30353 · Cited by 827 · see citing works
Vermeulen, L., Wilde, G. D., Damme, P. V., Berghe, W. V., & Haegeman, G. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg139 · Cited by 760 · see citing works
SUMO-1 Conjugation in Vivo Requires Both a Consensus Modification Motif and Nuclear Targeting
Rodríguez, M. S., Dargemont, C., & Hay, R. T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009476200 · Cited by 753 · see citing works
IκB-β regulates the persistent response in a biphasic activation of NF-κB
Thompson, J. E., Phillips, R. J., Erdjument‐Bromage, H., Tempst, P., & Ghosh, S. (1995) · Cell · doi:10.1016/0092-8674(95)90511-1 · Cited by 752 · see citing works
Sun, L., Deng, L., Ea, C.-K., Xia, Z.-P., & Chen, Z. J. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00236-9 · Cited by 700 · see citing works
Tyrosine Phosphorylation of IκB-α Activates NF-κB without Proteolytic Degradation of IκB-α
Imbert, V., Rupec, R. A., Livolsi, A., Pahl, H. L., Traenckner, E. B.-M., Mueller‐Dieckmann, C., Farahifar, D., Rossi, B., Auberger, P., Baeuerle, P. A., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)80153-1 · Cited by 660 · see citing works
Ryo, A., Suizu, F., Yoshida, Y., Perrem, K., Liou, Y., Wulf, G. M., Rottapel, R. K., Yamaoka, S., & Lu, K. P. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00490-8 · Cited by 632 · see citing works
IKKα limits macrophage NF-κB activation and contributes to the resolution of inflammation
Lawrence, T., Bébien, M., Liu, G. Y., Nizet, V., & Karin, M. (2005) · Nature · doi:10.1038/nature03491 · Cited by 625 · see citing works
Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-κB activation
Wu, C.-J., Conze, D. B., Li, T., Srinivasula, S. M., & Ashwell, J. D. (2006) · Nature Cell Biology · doi:10.1038/ncb1384 · Cited by 607 · see citing works
Huang, T. T., Wuerzberger‐Davis, S. M., Wu, Z., & Miyamoto, S. (2003) · Cell · doi:10.1016/s0092-8674(03)00895-x · Cited by 560 · see citing works
NF-κB-inducing kinase activates IKK-α by phosphorylation of Ser-176
Lei, L., Cao, Z., & Goeddel, D. V. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3792 · Cited by 536 · see citing works
Post-activation Turn-off of NF-κB-dependent Transcription Is Regulated by Acetylation of p65
Kiernan, R. E., Brès, V., Ng, R. W. M., Coudart, M.-P., Messaoudi, S. E., Sardet, C., Jin, D., Emiliani, S., & Benkirane, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209572200 · Cited by 536 · see citing works
Bcl10 activates the NF-κB pathway through ubiquitination of NEMO
Zhou, H., Wertz, I. E., O’Rourke, K. M., Ultsch, M. H., Seshagiri, S., Eby, M. T., Xiao, W., & Dixit, V. M. (2003) · Nature · doi:10.1038/nature02273 · Cited by 527 · see citing works
Kwok, B. H. B., Koh, B. D., Ndubuisi, M. I., Elofsson, M., & Crews, C. M. (2001) · Chemistry & Biology · doi:10.1016/s1074-5521(01)00049-7 · Cited by 516 · see citing works
Molecular Linkage Between the Kinase ATM and NF-κB Signaling in Response to Genotoxic Stimuli
Wu, Z., Shi, Y., Tibbetts, R. S., & Miyamoto, S. (2006) · Science · doi:10.1126/science.1121513 · Cited by 515 · see citing works
Takada, Y., Mukhopadhyay, A., Kundu, G. C., Mahabeleshwar, G. H., Singh, S., & Aggarwal, B. B. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212389200 · Cited by 495 · see citing works
Good cop, bad cop: the different faces of NF-κB
Perkins, N. D., & Gilmore, T. D. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401838 · Cited by 489 · see citing works
Self-citationInhibition of NF- B DNA Binding by Nitric Oxide
Matthews, J. R., Botting, C. H., Panico, M., Morris, H. R., & Hay, R. T. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.12.2236 · Cited by 489 · see citing works
Cyld Inhibits Tumor Cell Proliferation by Blocking Bcl-3-Dependent NF-κB Signaling
Massoumi, R., Masoumi, K. C., Hennecke, K., Pfeifer, A., & Fässler, R. (2006) · Cell · doi:10.1016/j.cell.2006.03.041 · Cited by 480 · see citing works
Wang, D., Westerheide, S. D., Ostrander, J. H., & Baldwin, A. S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001358200 · Cited by 454 · see citing works
NF-κB RelA Phosphorylation Regulates RelA Acetylation
Chen, L.-F., Williams, S. A., Mu, Y., Nakano, H., Duerr, J. M., Buckbinder, L., & Greene, W. C. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.18.7966-7975.2005 · Cited by 438 · see citing works
The essential role of MEKK3 in TNF-induced NF-κB activation
Yang, J., Lin, Y., Guo, Z., Cheng, J., Huang, J. H., Deng, L., Liao, W. S. ‐., Chen, Z. J., Liu, Z. G., & Su, B. (2001) · Nature Immunology · doi:10.1038/89769 · Cited by 396 · see citing works
I kappa B epsilon, a novel member of the IκB family, controls RelA and cRel NF‐κB activity
Whiteside, S. T., Epinat, J.-C., Rice, N. R., & Israël, A. (1997) · The EMBO Journal · doi:10.1093/emboj/16.6.1413 · Cited by 396 · see citing works
Sizemore, N., Lerner, N., Dombrowski, N., Sakurai, H., & Stark, G. R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110572200 · Cited by 391 · see citing works
Nitric oxide represses inhibitory κB kinase through S-nitrosylation
Reynaert, N. L., Ckless, K., Korn, S. H., Vos, N., Guala, A. S., Wouters, E. F. �., van der Vliet, A., & Janssen-Heininger, Y. M. W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400588101 · Cited by 388 · see citing works
Abbott, D. W., Wilkins, A., Asara, J. M., & Cantley, L. C. (2004) · Current Biology · doi:10.1016/j.cub.2004.12.032 · Cited by 374 · see citing works
Buss, H., Dörrie, A., Schmitz, M. L., Hoffmann, E., Resch, K., & Kracht, M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409825200 · Cited by 362 · see citing works
Phosphorylation of RelA/p65 on Serine 536 Defines an IκBα-independent NF-κB Pathway
Sasaki, C. Y., Barberi, T. J., Ghosh, P., & Longo, D. L. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504943200 · Cited by 330 · see citing works
Essential role of RelA Ser311 phosphorylation by ζPKC in NF‐κB transcriptional activation
Duran, A., Díaz-Meco, M. T., & Moscat, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg370 · Cited by 319 · see citing works
CK2 Is a C-Terminal IκB Kinase Responsible for NF-κB Activation during the UV Response
Kato, T., Delhase, M., Hoffmann, A., & Karin, M. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00358-7 · Cited by 313 · see citing works
Cotranslational Biogenesis of NF-κB p50 by the 26S Proteasome
Li, L., Demartino, G., & Greene, W. C. (1998) · Cell · doi:10.1016/s0092-8674(00)81409-9 · Cited by 312 · see citing works
Xiao, G., Fong, A., & Sun, S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401428200 · Cited by 296 · see citing works
Deng, W., Tang, S.-T., Tseng, H.-P., & Wu, K. K. (2006) · Blood · doi:10.1182/blood-2005-09-3691 · Cited by 267 · see citing works
Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3
Huang, Q., Yang, J., Lin, Y., Walker, C., Cheng, J., Liu, Z.-G., & Su, B. (2003) · Nature Immunology · doi:10.1038/ni1014 · Cited by 266 · see citing works
Schoonbroodt, S., Ferreira, V., Best-Belpomme, M., Boelaert, J. R., Legrand-Poels, S., Korner, M., & Piette, J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.8.4292 · Cited by 263 · see citing works
Bohuslav, J., Chen, L., Kwon, H., Mu, Y., & Greene, W. C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313509200 · Cited by 256 · see citing works
Phosphorylation of Serine 468 by GSK-3β Negatively Regulates Basal p65 NF-κB Activity
Buss, H., Dörrie, A., Schmitz, M. L., Frank, R., Livingstone, M., Resch, K., & Kracht, M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400442200 · Cited by 253 · see citing works
PDK1 Nucleates T Cell Receptor-Induced Signaling Complex for NF-κB Activation
Lee, K., D’Acquisto, F., Hayden, M. S., Shim, J., & Ghosh, S. (2005) · Science · doi:10.1126/science.1107107 · Cited by 253 · see citing works
Saccani, S., Marazzi, I., Beg, A. A., & Natoli, G. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040196 · Cited by 253 · see citing works
Mattioli, I., Sebald, A., Bucher, C., Charles, R., Nakano, H., Doi, T., Kracht, M., & Schmitz, M. L. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.10.6336 · Cited by 230 · see citing works
SMRT Derepression by the IκB Kinase α
Hoberg, J. E., Yeung, F., & Mayo, M. W. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.10.010 · Cited by 220 · see citing works
Regulation at multiple levels of NF-κB-mediated transactivation by protein acetylation
Quivy, V., & Lint, C. M. V. (2004) · Biochemical Pharmacology · doi:10.1016/j.bcp.2004.05.039 · Cited by 219 · see citing works
Tang, E., Wang, C.-Y., Xiong, Y., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303389200 · Cited by 206 · see citing works
Gustin, J. A., Özeş, O. N., Akça, H., Pincheira, R., Mayo, L. D., Li, Q., Guzman, J. R., Korgaonkar, C. K., & Donner, D. B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306976200 · Cited by 199 · see citing works
Lin, R., Beauparlant, P., Makris, C., Meloche, S., & Hiscott, J. B. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.4.1401 · Cited by 198 · see citing works
McElhinny, J. A., Trushin, S. A., Bren, G. D., Chester, N., & Payá, C. V. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.3.899 · Cited by 187 · see citing works
Fan, C., Li, Q., Ross, D., & Engelhardt, J. F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m206718200 · Cited by 183 · see citing works
Jiang, X., Takahashi, N., Matsui, N., Tetsuka, T., & Okamoto, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208696200 · Cited by 171 · see citing works
Enhancement of Nuclear Factor-κB Acetylation by Coactivator p300 and HIV-1 Tat Proteins
Furia, B., Deng, L., Wu, K., Baylor, S., Kehn‐Hall, K., Hong Li, A., DONNELLY, R. J., Coleman, T., & Kashanchi, F. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m107848200 · Cited by 166 · see citing works
Haller, D., Russo, M. P., Sartor, R. B., & Jobin, C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205737200 · Cited by 165 · see citing works
Schwarz, E. M., Antwerp, D. V., & Verma, I. M. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.7.3554 · Cited by 163 · see citing works
Glycogen Synthase Kinase-3β Regulates NF-κB1/p105 Stability
Demarchi, F., Bertoli, C., Sandy, P., & Schneider, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305676200 · Cited by 162 · see citing works
Regulation of NF‐κB and p53 through activation of ATR and Chk1 by the ARF tumour suppressor
Rocha, S., Garrett, M. D., Campbell, K. J., Schumm, K., & Perkins, N. D. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600608 · Cited by 161 · see citing works
Self-citationGarcía‐Piñeres, A., Lindenmeyer, M. T., & Merfort, I. (2004) · Life Sciences · doi:10.1016/j.lfs.2004.01.024 · Cited by 146 · see citing works
Deng, W., Zhu, Y., & Wu, K. K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209286200 · Cited by 146 · see citing works
Abu‐Amer, Y., Ross, F. P., McHugh, K. P., Livolsi, A., Peyron, J., & Teitelbaum, S. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.45.29417 · Cited by 143 · see citing works
GSK3-Mediated BCL-3 Phosphorylation Modulates Its Degradation and Its Oncogenicity
Viatour, P., Dejardin, E., Warnier, M., Lair, F., Claudio, E., Bureau, F., Marine, J., Merville, M., Maurer, U., Green, D. R., et al. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.09.004 · Cited by 139 · see citing works
Bui, N. T., Livolsi, A., Peyron, J., & Prehn, J. H. M. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.4.753 · Cited by 134 · see citing works
Rho GDP Dissociation Inhibitor Protects Cancer Cells against Drug-Induced Apoptosis
Zhang, B., Zhang, Y., Dagher, M., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0175 · Cited by 133 · see citing works
βTrCP-Mediated Proteolysis of NF-κB1 p105 Requires Phosphorylation of p105 Serines 927 and 932
Lang, V., Janzen, J., Fischer, G. Z., et al. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.23.1.402-413.2003 · Cited by 132 · see citing works
IκB Kinase Is an Essential Component of the Tpl2 Signaling Pathway
Waterfield, M. R., Jin, W., Reiley, W. W., Zhang, M., & Sun, S. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.13.6040-6048.2004 · Cited by 131 · see citing works
A pervasive role of ubiquitin conjugation in activation and termination of IκB kinase pathways
Krappmann, D., & Scheidereit, C. (2005) · The EMBO Reports · doi:10.1038/sj.embor.7400380 · Cited by 128 · see citing works
Huang, W., Chen, J.-J., Chen, C., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208521200 · Cited by 127 · see citing works
Inducible Phosphorylation of NF-κB p65 at Serine 468 by T Cell Costimulation Is Mediated by IKKϵ
Mattioli, I., Geng, H. Z., Sebald, A., Hodel, M., Bucher, C., Kracht, M., & Schmitz, M. L. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m508045200 · Cited by 124 · see citing works
NF-κB1 p105 Negatively Regulates TPL-2 MEK Kinase Activity
Beinke, S., Deka, J., Lang, V., Belich, M. P., Walker, P. A., Howell, S. A., Smerdon, S. J., Gamblin, S. J., & Ley, S. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.14.4739-4752.2003 · Cited by 124 · see citing works
Singh, S., Darnay, B. G., & Aggarwal, B. B. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.49.31049 · Cited by 122 · see citing works
Yeh, P.-Y., Yeh, K., Chuang, S., Song, Y., & Cheng, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402362200 · Cited by 119 · see citing works
Ubiquitin, TAK1 and IKK: is there a connection?
Chen, Z. J., Bhoj, V, & Seth, R. B. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401869 · Cited by 115 · see citing works
Regulation of IκBβ Degradation
Weil, R., Laurent‐Winter, C., & Israël, A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.15.9942 · Cited by 112 · see citing works
β-TrCP binding and processing of NF-κB2/p100 involve its phosphorylation at serines 866 and 870
Liang, C., Zhang, M., & Sun, S. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2005.10.011 · Cited by 112 · see citing works
Na, H., & Surh, Y. (2006) · Molecular Carcinogenesis · doi:10.1002/mc.20225 · Cited by 111 · see citing works
Amir, R. E., Haecker, H., Karin, M., & Ciechanover, A. J. (2003) · Oncogene · doi:10.1038/sj.onc.1207366 · Cited by 109 · see citing works
Mosialos, G., HAMER, P. J., Capobianco, A. J., et al. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.12.5867 · Cited by 105 · see citing works
Tanaka, H., Fujita, N., & Tsuruo, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506235200 · Cited by 105 · see citing works
Guan, H., Hou, S., & Ricciardi, R. P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412180200 · Cited by 104 · see citing works
Nuclear Accumulation of cRel following C-Terminal phosphorylation by TBK1/IKKε
Harris, J., Olière, S., Sharma, S., Sun, Q., Lin, R., Hiscott, J. B., & Grandvaux, N. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.4.2527 · Cited by 102 · see citing works
Hu, J., & Colburn, N. H. (2005) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-04-0070 · Cited by 98 · see citing works
Regulation of Nuclear Factor κB Transactivation
Martín, Á. G., San-Antonio, B., & Fresno, M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011313200 · Cited by 96 · see citing works
Park, S. W., Huq, M. D. M., Hu, X., & Wei, L. (2005) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m400195-mcp200 · Cited by 95 · see citing works
Anrather, J., Racchumi, G., & Iadecola, C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409344200 · Cited by 93 · see citing works
Phosphorylation of Serine 337 of NF-κB p50 Is Critical for DNA Binding
Hou, S., Guan, H., & Ricciardi, R. P. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307971200 · Cited by 92 · see citing works
Chu, Z., McKinsey, T. A., Liu, L., Qi, X., & Ballard, D. W. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.11.5974 · Cited by 84 · see citing works
IKKβ phosphorylates p65 at S468 in transactivaton domain 2
Schwabe, R. F., & Sakurai, H. (2005) · The FASEB Journal · doi:10.1096/fj.05-3736fje · Cited by 84 · see citing works
Liang, M., Bardhan, S., Pace, E. A., Rosman, D. S., Beutler, J. A., Porco, J. A. J., & Gilmore, T. D. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.11.013 · Cited by 83 · see citing works
Cisplatin Mimics ARF Tumor Suppressor Regulation of RelA (p65) Nuclear Factor-κB Transactivation
Campbell, K. J., Witty, J., Rocha, S., & Perkins, N. D. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2234 · Cited by 77 · see citing works
Self-citationAkt Regulates Basal and Induced Processing of NF-κB2 (p100) to p52
Gustin, J. A., Korgaonkar, C. K., Pincheira, R., Li, Q., & Donner, D. B. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m507373200 · Cited by 76 · see citing works
Mukhopadhyay, A., Manna, S. K., & Aggarwal, B. B. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.12.8549 · Cited by 74 · see citing works
Marienfeld, R. B., Berberich‐Siebelt, F., Berberich, I., Denk, A., Serfling, E., & Neumann, M. (2001) · Oncogene · doi:10.1038/sj.onc.1204884 · Cited by 73 · see citing works
Martín, Á. G., & Fresno, M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m909396199 · Cited by 70 · see citing works
Fischer, C., Page, S., Weber, M., Eisele, T., Neumeier, D., & Brand, K. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.35.24625 · Cited by 67 · see citing works
Pellegatta, F., Bertelli, A. A. E., Staels, B., et al. (2003) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/77.5.1220 · Cited by 67 · see citing works
Liu, J., & Beller, D. I. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.1.581 · Cited by 67 · see citing works
Regulation of IκB Kinase (IKK)γ/NEMO Function by IKKβ-mediated Phosphorylation
Prajapati, S., & Gaynor, R. B. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201393200 · Cited by 60 · see citing works
Cohen, S., Achbert-Weiner, H., & Ciechanover, A. J. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.24.1.475-486.2004 · Cited by 60 · see citing works
Park, M. H., Song, H. S., Kim, K. H., et al. (2005) · Biochemistry · doi:10.1021/bi050156h · Cited by 57 · see citing works
Critical Role of RelB Serine 368 for Dimerization and p100 Stabilization
Maier, H. J., Marienfeld, R. B., Wirth, T., & Baumann, B. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301521200 · Cited by 57 · see citing works
Sánchez-Valdepeñas, C., Martín, Á. G., Ramakrishnan, P., Wallach, D., & Fresno, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.8.4666 · Cited by 56 · see citing works
Mahabeleshwar, G. H., & Kundu, G. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308941200 · Cited by 53 · see citing works
Druker, B. J., Neumann, M., Okuda, K., Franza, B. R., & Griffin, J. D. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37699-8 · Cited by 50 · see citing works
Miller, B. S., Higashimoto, T., Lee, Y.-K., & Zandi, E. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513793200 · Cited by 49 · see citing works
Phosphorylation of the PEST Domain of IκBβ Regulates the Function of NF-κB/IκBβ Complexes
McKinsey, T. A., Chu, Z., & Ballard, D. W. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.36.22377 · Cited by 49 · see citing works
Differential Phosphorylation of the Signal-responsive Domain of IκBα and IκBβ by IκB Kinases
Wu, C., & Ghosh, S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304278200 · Cited by 47 · see citing works
Carter, R. S., Pennington, K. N., Arrate, M. P., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508656200 · Cited by 38 · see citing works
Degradation of Proto-oncoprotein c-Rel by the Ubiquitin-Proteasome Pathway
Chen, E., Hrdličková, R., Nehyba, J., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.52.35201 · Cited by 35 · see citing works
In Vivo Identification of Inducible Phosphoacceptors in the IKKγ/NEMO Subunit of Human IκB Kinase
Carter, R. S., Pennington, K. N., Ungurait, B. J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301705200 · Cited by 35 · see citing works
Glineur, C., Davioud–Charvet, E., & Vandenbunder, B. (2000) · Biochemical Journal · doi:10.1042/bj3520583 · Cited by 35 · see citing works
Inflammatory Diseases: Is Ubiquitinated NEMO at the Hub?
Burns, K., & Martinon, F. (2004) · Current Biology · doi:10.1016/j.cub.2004.11.040 · Cited by 33 · see citing works
Babu, G. R., Jin, W., Norman, L. P., Waterfield, M. R., Chang, M., Wu, X., Zhang, M., & Sun, S. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2005.12.010 · Cited by 32 · see citing works
Stimulation of c-Rel transcriptional activity by PKA catalytic subunit ?
Yu, S.-H., Chiang, W., Shih, H.-M., & Wu, K.-J. (2004) · Journal of Molecular Medicine · doi:10.1007/s00109-004-0559-7 · Cited by 31 · see citing works
Starczynowski, D. T., Reynolds, J. G., & Gilmore, T. D. (2005) · Oncogene · doi:10.1038/sj.onc.1208902 · Cited by 26 · see citing works
Fognani, C., Rondi, R., Romano, A., & Blasi, F. (2000) · Oncogene · doi:10.1038/sj.onc.1203543 · Cited by 17 · see citing works
Kang, J. L., Lee, H. S., Pack, I. S., et al. (2003) · Molecular and Cellular Biochemistry · doi:10.1023/a:1024163630166 · Cited by 15 · see citing works
Gapuzan, M.-E. R., Pitoc, G. A., & Gilmore, T. D. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01123-9 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Integrating cell-signalling pathways with NF-κB and IKK function
Perkins, N. D. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2083 · Cited by 2,350 · see citing works
Self-citationLysine Acetylation: Codified Crosstalk with Other Posttranslational Modifications
Yang, X.-J., & Seto, E. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.07.002 · Cited by 1,006 · see citing works
Miller, G. E., Chen, E., Fok, A. K., Walker, H., Lim, A., Nicholls, E. F., Cole, S., & Kobor, M. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0902971106 · Cited by 822 · see citing works
Inhibiting NF-κB activation by small molecules as a therapeutic strategy
Gupta, S. C., Sundaram, C., Reuter, S., & Aggarwal, B. B. (2010) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2010.05.004 · Cited by 762 · see citing works
Regulation of hypoxia-inducible factor-1α by NF-κB
van Uden, P., Kenneth, N. S., & Rocha, S. (2008) · Biochemical Journal · doi:10.1042/bj20080476 · Cited by 729 · see citing works
Bubici, C., Papa, S., Dean, K., & Franzoso, G. (2006) · Oncogene · doi:10.1038/sj.onc.1209936 · Cited by 399 · see citing works
Beck, I. M. E., Vanden Berghe, W., Vermeulen, L., Yamamoto, K. R., Haegeman, G., & De Bosscher, K. (2009) · Endocrine Reviews · doi:10.1210/er.2009-0013 · Cited by 298 · see citing works
Beyond IκBs: alternative regulation of NF‐KB activity
Neumann, M., & Naumann, M. (2007) · The FASEB Journal · doi:10.1096/fj.06-7615rev · Cited by 267 · see citing works
ABINs: A20 binding inhibitors of NF-κB and apoptosis signaling
Verstrepen, L., Carpentier, I., Verhelst, K., & Beyaert, R. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.02.009 · Cited by 180 · see citing works
Evolutionary Conserved Regulation of HIF-1β by NF-κB
van Uden, P., Kenneth, N. S., Webster, R., Müller, H. A., Mudie, S., & Rocha, S. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001285 · Cited by 163 · see citing works
Rodríguez-Calvo, R., Tajes, M., & Vázquez-Carrera, M. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2017.1279146 · Cited by 117 · see citing works
Ku, C. S., Pham, T. X., Park, Y., Kim, B., Shin, M. S., Kang, I., & Lee, J. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.01.018 · Cited by 109 · see citing works
Targeting the acetylation signaling pathway in cancer therapy
Dang, F., & Wei, W. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.03.001 · Cited by 109 · see citing works
Intermolecular disulfide bond formation in the nemo dimer requires cys54 and cys347
Herscovitch, M., Comb, W., Ennis, T., Coleman, K., Yong, S., Armstead, B., Kalaitzidis, D., Chandani, S., & Gilmore, T. D. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.12.123 · Cited by 89 · see citing works
Heida, A., Gruben, N., Catrysse, L., Koehorst, M., Koster, M., Kloosterhuis, N. J., Gerding, A., Havinga, R., Bloks, V. W., Bongiovanni, L., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101349 · Cited by 78 · see citing works
Atkinson, G. P., Nozell, S. E., Harrison, D. K., Stonecypher, M. S., Chen, D., & Benveniste, E. N. (2009) · Oncogene · doi:10.1038/onc.2009.232 · Cited by 75 · see citing works
Yao, H., Yan, J., Yin, L., & Chen, W. (2022) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2022.2054425 · Cited by 17 · see citing works
- Authors
- Perkins, N. D.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- Perkins, N D
- ORCID
- Perkins, N D
- Venue
- Oncogene
- Published
- 2006-10-30
- Volume
- 25
- Issue
- 51
- Pages
- 6717-6730
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W1999982643
- Cited by
- 674
- References
- 137
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 16 · 2023: 13 · 2022: 24 · 2021: 45 · 2020: 24 · 2019: 28 · 2018: 32 · 2017: 49 · 2016: 31 · 2015: 33 · 2014: 52 · 2013: 38 · 2012: 41
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Keywords
- NF-κB signaling, post-translational modification, IκB kinase complex, IκB proteins, NF-κB subunits, phosphorylation, ubiquitination, acetylation, SUMOylation, nitrosylation, therapeutic target, biomarkers
- MeSH terms
- Animals, Cell Nucleus, Cytoplasm, Enzyme Activation, Humans, Hydrolysis, Protein Processing, Post-Translational, NF-kappa B, I-kappa B Kinase
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
