A pervasive role of ubiquitin conjugation in activation and termination of IκB kinase pathways
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The nuclear factor (NF)-kappaB pathway is a paradigm for gene expression control by ubiquitin-mediated protein degradation. In stimulated cells, phosphorylation by the IkappaB kinase (IKK) complex primes NF-kappaB-inhibiting IkappaB molecules for lysine (Lys)-48-linked polyubiquitination and subsequent destruction by the 26S proteasome. However, recent studies indicate that the ubiquitin (Ub) system controls NF-kappaB pathways at many levels. Ub ligases are activated by different upstream signalling pathways, and they function as central regulators of IKK and c-Jun amino-terminal kinase activation. The assembly of Lys 63 polyUb chains provides docking surfaces for the recruitment of IKK-activating complexes, a reaction that is counteracted by deubiquitinating enzymes. Furthermore, Ub conjugation targets upstream signalling mediators as well as nuclear NF-kappaB for post-inductive degradation to limit the duration of signalling.
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Inflammatory signals such as LPS, pro-inflammatory cytokines, reactive oxygen species, advanced glycation end products, and oxidized LDL cause IKKβ phosphorylation; this phosphorylates IκBα, leading to its ubiquitination and degradation, which releases NF-κB to enter the nucleus and induce pro-inflammatory genes.
“Extracellular inflammatory signals including lipopolysaccharide (LPS), pro-inflammatory cytokines, reactive oxygen species, advanced glycation end products, and oxidized low-density lipoprotein trigger the phosphorylation of IKKβ, which in turn phosphorylates IκBα for ubiquitination and degradation by proteasome [13–18].”
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 [15]
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Hayden, M. S., & Ghosh, S. (2004) · Genes & Development · doi:10.1101/gad.1228704 · Cited by 3,842 · 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
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
Deng, L., Wang, C., Spencer, E., Yang, L., Braun, A., You, J., Slaughter, C., Pickart, C., & Chen, Z. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00126-4 · Cited by 1,872 · see citing works
De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling
Wertz, I. E., O’Rourke, K. M., Zhou, H., Eby, M. T., Aravind, L., Seshagiri, S., Wu, P., Wiesmann, C., Baker, R. T., Boone, D. L., et al. (2004) · Nature · doi:10.1038/nature02794 · Cited by 1,852 · see citing works
Failure to Regulate TNF-Induced NF-κB and Cell Death Responses in A20-Deficient Mice
Lee, E. G., Boone, D. L., Chai, S., Libby, S. L., Chien, M., Lodolce, J. P., & Ma, A. (2000) · Science · doi:10.1126/science.289.5488.2350 · Cited by 1,409 · see citing works
TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signalingPreprint
Lomaga, M. A., Yeh, W., Sarosi, I., Duncan, G. S., Furlonger, C. L., Ho, A. P., Morony, S., Capparelli, C., Van, G. Y., Kaufman, S., et al. (1999) · Genes & Development · doi:10.1101/gad.13.8.1015 · Cited by 1,253 · see citing works
Ninomiya‐Tsuji, J., Kishimoto, K., Hiyama, A., Inoue, J., Cao, Z., & Matsumoto, K. (1999) · Nature · doi:10.1038/18465 · Cited by 1,187 · see citing works
The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses
Boone, D. L., Turer, E. E., Lee, E. G., Ahmad, R., Wheeler, M. T., Tsui, C., Hurley, P. J., Chien, M., Chai, S., Hitotsumatsu, O., et al. (2004) · Nature Immunology · doi:10.1038/ni1110 · Cited by 1,086 · see citing works
The tumour suppressor CYLD negatively regulates NF-κB signalling by deubiquitination
Kovalenko, A., Chable-Bessia, C., Cantarella, G., Israël, A., Wallach, D., & Courtois, G. (2003) · Nature · doi:10.1038/nature01802 · Cited by 1,018 · see citing works
CYLD is a deubiquitinating enzyme that negatively regulates NF-κB activation by TNFR family members
Trompouki, E., Hatzivassiliou, E., Tsichritzis, T., Farmer, H., Ashworth, A., & Mosialos, G. (2003) · Nature · doi:10.1038/nature01803 · Cited by 964 · see citing works
Site-Specific Phosphorylation of IκBα by a Novel Ubiquitination-Dependent Protein Kinase Activity
Chen, Z. J., Parent, L. A., & Maniatis, T. (1996) · Cell · doi:10.1016/s0092-8674(00)81064-8 · Cited by 958 · see citing works
Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-κB
Brummelkamp, T. R., Nijman, S. M. B., Dirac, A. M. G., & Bernards, R. (2003) · Nature · doi:10.1038/nature01811 · Cited by 947 · see citing works
TAB2 and TAB3 Activate the NF-κB Pathway through Binding to Polyubiquitin Chains
Kanayama, A., Seth, R. B., Sun, L., Ea, C.-K., Hong, M., Shaito, A. A., Chiu, Y., Deng, L., & Chen, Z. J. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.08.008 · Cited by 890 · see citing works
Seibenhener, M. L., Babu, J. R., Geetha, T., Wong, H. C., Krishna, N. R., & Wooten, M. W. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.18.8055-8068.2004 · Cited by 710 · 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
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
Baek, S. H., Ohgi, K., Rose, D., Koo, E., Glass, C., & Rosenfeld, M. (2002) · Cell · doi:10.1016/s0092-8674(02)00809-7 · Cited by 591 · 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
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
Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins
Heissmeyer, V., Macián, F., Im, S., Varma, R., Feske, S., Venuprasad, K., Gu, H., Liu, Y., Dustin, M. L., & Rao, A. (2004) · Nature Immunology · doi:10.1038/ni1047 · Cited by 515 · see citing works
Recruitment of TNF Receptor 1 to Lipid Rafts Is Essential for TNFα-Mediated NF-κB Activation
Legler, D. F., Micheau, O., Doucey, M., Tschopp, J., & Bron, C. (2003) · Immunity · doi:10.1016/s1074-7613(03)00092-x · Cited by 464 · see citing works
TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2
Li, X., Yang, Y., & Ashwell, J. D. (2002) · Nature · doi:10.1038/416345a · Cited by 452 · see citing works
The atypical PKC‐interacting protein p62 channels NF‐κB activation by the IL‐1–TRAF6 pathway
Sanz, L., Diaz‐Meco, M. T., Nakano, H., & Moscat, J. (2000) · The EMBO Journal · doi:10.1093/emboj/19.7.1576 · Cited by 436 · see citing works
Lucas, P. C., Yonezumi, M., Inohara, N., McAllister‐Lucas, L. M., Abazeed, M. E., Chen, F. F., Yamaoka, S., Seto, M., & Núñez, G. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009984200 · Cited by 417 · see citing works
TAK1 is Critical for IκB Kinase-mediated Activation of the NF-κB Pathway
Takaesu, G., Surabhi, R. M., Park, K.-J., Ninomiya‐Tsuji, J., Matsumoto, K., & Gaynor, R. B. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)01404-3 · Cited by 404 · see citing works
CARMA1, BCL-10 and MALT1 in lymphocyte development and activation
Thome, M. (2004) · Nature Reviews Immunology · doi:10.1038/nri1352 · Cited by 391 · 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
The hPLIC Proteins May Provide a Link between the Ubiquitination Machinery and the Proteasome
Kleijnen, M. F., Shih, A. H., Zhou, P., Kumar, S., Soccio, R. E., Kedersha, N., Gill, G., & Howley, P. M. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00040-x · Cited by 352 · see citing works
Durán, A., Serrano, M., Leitges, M., Flores, J. M., Picard, S., Brown, J. P., Moscat, J., & Diaz-Meco, M. T. (2004) · Developmental Cell · doi:10.1016/s1534-5807(03)00403-9 · Cited by 316 · see citing works
Tada, K., Okazaki, T., Sakon, S., Kobarai, T., Kurosawa, K., Yamaoka, S., Hashimoto, H., Mak, T. W., Yagita, H., Okumura, K., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104837200 · Cited by 306 · see citing works
Role of the TAB2‐related protein TAB3 in IL‐1 and TNF signaling
Ishitani, T., Takaesu, G., Ninomiya‐Tsuji, J., Shibuyà, H., Gaynor, R. B., & Matsumoto, K. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg605 · Cited by 273 · 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
Requirement of NF-κB/Rel for the development of hair follicles and other epidermal appendices
Schmidt-Ullrich, R., Aebischer, T., Hülsken, J., Birchmeier, W., Klemm, U., & Scheidereit, C. (2001) · Development · doi:10.1242/dev.128.19.3843 · Cited by 216 · see citing works
Self-citationUbiquitination and translocation of TRAF2 is required for activation of JNK but not of p38 or NF‐κB
Habelhah, H., Takahashi, S., Cho, S., Kadoya, T., Watanabe, T., & Ronai, Z. A. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600044 · Cited by 207 · see citing works
NF-κB Is Essential for Induction of CYLD, the Negative Regulator of NF-κB
Jono, H., Lim, J. H., Chen, L. F., Xu, H., Trompouki, E., Pan, Z. K., Mosialos, G., & Li, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406638200 · Cited by 180 · see citing works
Shi, C.-S., & Kehrl, J. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211796200 · Cited by 174 · see citing works
Negative Regulation of JNK Signaling by the Tumor Suppressor CYLD
Reiley, W. W., Zhang, M., & Sun, S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m411049200 · Cited by 148 · see citing works
Degradation of Bcl10 Induced by T-Cell Activation Negatively Regulates NF-κB Signaling
Scharschmidt, E., Wegener, E., Heissmeyer, V., Rao, A., & Krappmann, D. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.9.3860-3873.2004 · Cited by 145 · see citing works
Self-citationTIFA activates IκB kinase (IKK) by promoting oligomerization and ubiquitination of TRAF6
Ea, C.-K., Sun, L., Inoue, J., & Chen, Z. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404132101 · Cited by 129 · see citing works
Isolation and characterization of two novel A20-like proteins
Evans, P. C., TAYLOR, E. R., Coadwell, J., Heyninck, K., Beyaert, R., & Kilshaw, P. J. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3570617 · Cited by 90 · see citing works
Isolation and characterization of two novel A20-like proteins
Evans, P. C., TAYLOR, E. R., Coadwell, J., et al. (2001) · Biochemical Journal · doi:10.1042/bj3570617 · Cited by 73 · see citing works
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The NF- B Family of Transcription Factors and Its RegulationPreprint
Oeckinghaus, A., & Ghosh, S. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a000034 · Cited by 2,850 · see citing works
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
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
Nonproteolytic Functions of Ubiquitin in Cell Signaling
Chen, Z. J., & Sun, L. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.01.014 · Cited by 921 · see citing works
Ubiquitylation and cell signaling
Haglund, K., & Đikić, I. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600808 · Cited by 736 · see citing works
Perkins, N. D. (2006) · Oncogene · doi:10.1038/sj.onc.1209937 · Cited by 674 · see citing works
Reading protein modifications with interaction domains
Seet, B. T., Đikić, I., Zhou, M., & Pawson, T. J. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1960 · Cited by 662 · see citing works
IκB kinase complexes: gateways to NF-κB activation and transcription
Scheidereit, C. (2006) · Oncogene · doi:10.1038/sj.onc.1209934 · Cited by 648 · see citing works
Self-citationUbiquitylation in innate and adaptive immunity
Bhoj, V. G., & Chen, Z. J. (2009) · Nature · doi:10.1038/nature07959 · Cited by 632 · see citing works
Direct activation of protein kinases by unanchored polyubiquitin chains
Xia, Z.-P., Sun, L., Chen, X., Pineda, G., Jiang, X., Adhikari, A., Zeng, W., & Chen, Z. J. (2009) · Nature · doi:10.1038/nature08247 · Cited by 570 · see citing works
The Role of Ubiquitin in NF-κB Regulatory Pathways
Skaug, B. A., Jiang, X., & Chen, Z. J. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.070907.102750 · Cited by 471 · see citing works
Ubiquitin-mediated activation of TAK1 and IKK
Adhikari, A., Xu, M., & Chen, Z. J. (2007) · Oncogene · doi:10.1038/sj.onc.1210413 · Cited by 455 · see citing works
The tumour suppressor CYLD is a negative regulator of RIG‐I‐mediated antiviral response
Friedman, C. S., O’Donnell, M. A., Legarda, D., Ng, A., Cardenas, W. B., Yount, J. S., Moran, T. M., Basler, C. F., Komuro, A., Horvath, C. M., et al. (2008) · EMBO Reports · doi:10.1038/embor.2008.136 · Cited by 334 · see citing works
Aging alters tissue resident mesenchymal stem cell properties
Alt, E. U., Senst, C., Murthy, S. N., Slakey, D. P., Dupin, C. L., Chaffin, A. E., Kadowitz, P. J., & Izadpanah, R. (2012) · Stem Cell Research · doi:10.1016/j.scr.2011.11.002 · Cited by 316 · see citing works
Apoptotic and non-apoptotic programmed cardiomyocyte death in ventricular remodelling
Dorn, G. W. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn243 · Cited by 301 · see citing works
Christmann, M., & Kaina, B. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt635 · Cited by 245 · see citing works
Xu, M., Skaug, B. A., Zeng, W., & Chen, Z. J. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.10.002 · Cited by 246 · see citing works
Modulation of the Interferon Antiviral Response by the TBK1/IKKi Adaptor Protein TANK
Guo, B., & Cheng, G. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700017200 · Cited by 221 · see citing works
NF‐κB regulation: lessons from structures
Ghosh, G., Wang, V. Y., Huang, D., & Fusco, A. J. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01097.x · Cited by 209 · see citing works
Roles of NF-κB in health and disease: mechanisms and therapeutic potential
Wong, E. T., & Tergaonkar, V. (2009) · Clinical Science · doi:10.1042/cs20080502 · Cited by 195 · see citing works
Parkin Mediates Neuroprotection through Activation of IκB Kinase/Nuclear Factor-κB Signaling
Henn, I. H., Bouman, L., Schlehe, J. S., Schlierf, A., Schramm, J. E., Wegener, E., Nakaso, K., Culmsee, C., Berninger, B., Krappmann, D., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.5537-06.2007 · Cited by 188 · see citing works
Self-citationDimerization and Ubiquitin Mediated Recruitment of A20, a Complex Deubiquitinating Enzyme
Lu, T. T., Onizawa, M., Hammer, G. E., Turer, E. E., Yin, Q., Damko, E., Agelidis, A. M., Shifrin, N. T., Advincula, R., Barrera, J., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.03.008 · Cited by 185 · see citing works
Sha, D., Chin, L., & Li, L. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp501 · Cited by 180 · see citing works
The ubiquitin-proteasome system in cardiac physiology and pathology
Powell, S. R. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00062.2006 · Cited by 173 · see citing works
Hutti, J. E., Turk, B. E., Asara, J. M., Ma, A. I., Cantley, L. C., & Abbott, D. W. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01101-07 · Cited by 169 · see citing works
Visekruna, A., Joeris, T., Seidel, D., Kroesen, A. J., Loddenkemper, C., Zeitz, M., Kaufmann, S. H. E., Schmidt‐Ullrich, R., & Steinhoff, U. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28804 · Cited by 159 · see citing works
Geng, H. Z., Wittwer, T., Dittrich‐Breiholz, O., Kracht, M., & Schmitz, M. L. (2009) · EMBO Reports · doi:10.1038/embor.2009.10 · Cited by 155 · see citing works
Nuclear IKK activity leads to dysregulated Notch-dependent gene expression in colorectal cancer
Fernández‐Majada, V., Aguilera, C., Villanueva, A., Vilardell, F., Robert‐Moreno, A., Aytés, À., Real, F. X., Capellá, G., Mayo, M. W., Espinosa, L., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606476104 · Cited by 141 · see citing works
Sunami, Y., Leithäuser, F., Gul, S., Fiedler, K., Güldiken, N., Espenlaub, S., Holzmann, K., Hipp, N., Sindrilaru, A., Luedde, T., et al. (2012) · Hepatology · doi:10.1002/hep.25711 · Cited by 133 · see citing works
Negrate, G. L., Krieg, A. H., Faustin, B., Loeffler, M. W., Godzik, A., Krajewski, S., & Reed, J. C. (2008) · Cellular Microbiology · doi:10.1111/j.1462-5822.2008.01178.x · Cited by 114 · see citing works
Ubiquitin Lysine 63 Chain–Forming Ligases Regulate Apical Dominance inArabidopsis
Yin, X., Volk, S., Ljung, K., Mehlmer, N., Doležal, K., Ditengou, F. A., Hanano, S., Davis, S. J., Schmelzer, E., Sandberg, G., et al. (2007) · The Plant Cell · doi:10.1105/tpc.107.052035 · Cited by 114 · 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
Inactivation of the CYLD Deubiquitinase by HPV E6 Mediates Hypoxia-Induced NF-κB Activation
An, J., Mo, D., Liu, H., Veena, M. S., Srivatsan, E. S., Massoumi, R., & Rettig, M. B. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.10.007 · Cited by 110 · see citing works
Huh, J. R., Foe, I. T., Muro, I., Chen, C., Seol, J. H., Yoo, S. J., Guo, M., Park, J. M., & Hay, B. A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608051200 · Cited by 97 · see citing works
Potential Roles for Ubiquitin and the Proteasome during Ribosome Biogenesis
Stavreva, D. A., Kawasaki, M., Dundr, M., Koberna, K., Müller, W. G., Tsujimura-Takahashi, T., Komatsu, W., Hayano, T., Isobe, T., Raška, I., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.02227-05 · Cited by 96 · see citing works
Jin, X., Jin, H. R., Jung, H. S., Lee, S. J., Lee, J.-H., & Lee, J. J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.129551 · Cited by 94 · see citing works
RUNX2-modifying enzymes: therapeutic targets for bone diseases
Kim, W., Shin, H.-L., Kim, B. S., Kim, H., & Ryoo, H. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0471-4 · Cited by 96 · see citing works
NFκB/p53 crosstalk—a promising new therapeutic target
Schneider, G., & Krämer, O. H. (2011) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2010.10.003 · Cited by 87 · see citing works
Is the ubiquitin-proteasome system impaired in Huntington’s disease?
Ortega, Z., Dı́az-Hernández, M., & Lucas, J. J. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7222-8 · Cited by 85 · see citing works
Deubiquitylating enzymes and disease
Singhal, S., Taylor, M. C., & Baker, R. T. (2008) · BMC Biochemistry · doi:10.1186/1471-2091-9-s1-s3 · Cited by 85 · see citing works
Zheng, Z., Li, H., Zhang, Z., Meng, J., Mao, D., Bai, B., Lu, B., Mao, P., Hu, Q., & Wang, H. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100285 · Cited by 85 · see citing works
The ubiquitin proteasome system and myocardial ischemia
Calise, J., & Powell, S. R. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00604.2012 · Cited by 70 · see citing works
Elia, A., Constantinou, C., & Clemens, M. J. (2007) · Oncogene · doi:10.1038/sj.onc.1210678 · Cited by 67 · see citing works
Zinc oxide particles induce inflammatory responses in vascular endothelial cells via NF-κB signaling
Tsou, T., Yeh, S., Tsai, F., Lin, H.-J., Cheng, T., Chao, H., & Tai, L. (2010) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2010.07.010 · Cited by 66 · see citing works
Żmijewski, J. W., Zhao, X., Xu, Z., & Abraham, E. H. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00618.2006 · Cited by 64 · see citing works
Rosato, R. R., Kolla, S. S., Hock, S. K., Almenara, J. A., Patel, A. K., Amin, S., Atadja, P. W., Fisher, P. B., Dent, P., & Grant, S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.095208 · Cited by 64 · see citing works
RetractedChiu, Y., Zhao, M., & Chen, Z. J. (2009) · Chemical Reviews · doi:10.1021/cr800554j · Cited by 64 · see citing works
Temporal resolution of two-tracked NF-κB activation byLegionella pneumophila
Bartfeld, S., Engels, C., Bauer, B., Auraß, P., Flieger, A., Brüggemann, H., & Meyer, T. F. (2009) · Cellular Microbiology · doi:10.1111/j.1462-5822.2009.01354.x · Cited by 63 · see citing works
IκB Kinase ε Phosphorylates TRAF2 To Promote Mammary Epithelial Cell Transformation
Shen, R. R., Zhou, A. Y., Kim, E., Lim, E., Habelhah, H., & Hahn, W. C. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00468-12 · Cited by 60 · see citing works
Panahi, Y., Darvishi, B., Ghanei, M., Jowzi, N., Beiraghdar, F., & Varnamkhasti, B. S. (2016) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2015.12.004 · Cited by 62 · see citing works
The effect of proteasome inhibitor MG132 on experimental inflammatory bowel disease
Inoue, S., Nakase, H., Matsuura, M., Mikami, S., Ueno, S., Uza, N., & Chiba, T. (2009) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2008.03872.x · Cited by 60 · see citing works
An RNAi screen identifies USP2 as a factor required for TNF‐α‐induced NF‐κB signaling
Metzig, M. O., Nickles, D., Falschlehner, C., Lehmann‐Koch, J., Straub, B. K., Roth, W., & Boutros, M. (2011) · International Journal of Cancer · doi:10.1002/ijc.26124 · Cited by 55 · see citing works
Mao, X. R., Moerman-Herzog, A. M., Chen, Y., & Barger, S. W. (2009) · Journal of Neuroinflammation · doi:10.1186/1742-2094-6-16 · Cited by 54 · 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
Combined Effect of Proteasome and Calpain Inhibition on Cisplatin-Resistant Human Melanoma Cells
Młynarczuk-Biały, I., Röckmann, H., Kuckelkorn, U., Schmidt, B., Umbreen, S., Gołąb, J., Ludwig, A., Montag, C., Wiebusch, L., Hagemeier, C., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2614 · Cited by 48 · see citing works
Ear, T., Fortin, C. F., Simard, F. A., & McDonald, P. P. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902958 · Cited by 46 · see citing works
Post-translational control of NF-κB signaling by ubiquitination
Won, M., Byun, H. S., Park, K. A., & Hur, G. M. (2016) · Archives of Pharmacal Research · doi:10.1007/s12272-016-0772-2 · Cited by 41 · see citing works
Grillari, J., Katinger, H. W. D., & Voglauer, R. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.07.003 · Cited by 40 · see citing works
Substrate selection by the proteasome through initiation regions
Tomita, T., & Matouschek, A. T. (2019) · Protein Science · doi:10.1002/pro.3642 · Cited by 37 · see citing works
Grillari, J., Grillari‐Voglauer, R., & Jansen‐Dürr, P. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-7002-2_13 · Cited by 34 · see citing works
COVID-19 and Parkinson’s Disease: Shared Inflammatory Pathways Under Oxidative Stress
Chaudhry, Z. L., Klenja, D., Janjua, N. A., Cami‐Kobeci, G., & Ahmed, B. Y. (2020) · Brain Sciences · doi:10.3390/brainsci10110807 · Cited by 35 · see citing works
Tsou, T., Liou, S.-H., Yeh, S., Tsai, F., & Chao, H. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.09.014 · Cited by 32 · see citing works
WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-κB activation pathway
Gao, D., Wang, R., Li, B., Yang, Y., Zhai, Z., & Chen, D. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0059-6 · Cited by 31 · see citing works
Jing, H., Shen, G., Wang, G., Zhang, F., Li, Y., Luo, F., Yao, J., & Tian, X. (2011) · Journal of Surgical Research · doi:10.1016/j.jss.2011.09.001 · Cited by 31 · see citing works
The Nuclear Factor-κB Pathway Regulates Cytochrome P450 3A4 Protein Stability
Zangar, R. C., Bollinger, N., Verma, S., Karin, N. J., & Lu, Y. W. (2008) · Molecular Pharmacology · doi:10.1124/mol.107.043976 · Cited by 30 · see citing works
SCFβTrCP1 Activates and Ubiquitylates TAp63γ
Gallegos, J. R., Litersky, J. M., Lee, H., Sun, Y., Nakayama, K., Nakayama, K., & Lu, H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704686200 · Cited by 29 · see citing works
NF-κB: The Inducible Factors of HIV-1 Transcription and their Inhibitors
Yu, M., Xinyong, L., & Clercq, E. D. (2008) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/138955709787001677 · Cited by 29 · see citing works
The parkin protein as a therapeutic target in Parkinson's disease
Winklhofer, K. F. (2007) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.11.12.1543 · Cited by 27 · see citing works
Higashimoto, T., Chan, N., Lee, Y.-K., & Zandi, E. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806258200 · Cited by 27 · see citing works
HSCARG Regulates NF-κB Activation by Promoting the Ubiquitination of RelA or COMMD1
Lian, M., & Zheng, X. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m809752200 · Cited by 26 · see citing works
Alternative UPS drug targets upstream the 26S proteasome
Hjerpe, R., & Rodríguez, M. S. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.11.021 · Cited by 24 · see citing works
Noh, E., Lee, Y., Hong, O., Jung, S. H., Youn, H. J., & Kim, J. (2015) · Oncology Reports · doi:10.3892/or.2015.4027 · Cited by 23 · see citing works
Zinc induces chemokine and inflammatory cytokine release from human promonocytes
Tsou, T., Chao, H., Yeh, S., Tsai, F., & Lin, H.-J. (2011) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2011.09.035 · Cited by 23 · see citing works
Han, Y., Li, R., Gao, J., Miao, S., & Wang, L. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.10.109 · Cited by 21 · see citing works
Dynamic Protein Complexes Regulate NF-κB Signaling
Wegener, E., & Krappmann, D. (2008) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-72843-6_10 · Cited by 21 · see citing works
Self-citationLiterature-related discovery: common factors for Parkinson’s Disease and Crohn’s Disease
Kostoff, R. N. (2014) · Scientometrics · doi:10.1007/s11192-014-1298-3 · Cited by 21 · see citing works
Bychkova, V. E., Dolgikh, D. A., Balobanov, V. A., & Finkelstein, A. V. (2022) · Molecules · doi:10.3390/molecules27144361 · Cited by 20 · see citing works
Zhang, Z., Yang, Z., Wang, S., Wang, X., & Mao, J. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117367 · Cited by 21 · see citing works
Ubiquitin Ligases in Cancer: Ushers for Degradation
Newton, K., & Vucic, D. (2007) · Cancer Investigation · doi:10.1080/07357900701508041 · Cited by 20 · see citing works
Zhao, X., Pu, D.-B., Zhao, Z., Zhu, H., Li, H., Shen, Y., Zhang, X., Zhang, R., Shen, J., Xiao, W., et al. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00565 · Cited by 18 · see citing works
Role of Monoubiquitylation on the Control of IκBα Degradation and NF-κB Activity
Silva-Ferrada, E. D., Torres-Ramos, M., Aillet, F., Campagna, M., Matute, C., Rivas, C., Rodríguez, M. S., & Lang, V. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025397 · Cited by 18 · see citing works
Protein Kinase-Mediated Decision Between the Life and Death
Engin, A. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-49844-3_1 · Cited by 17 · see citing works
Innate link between NF-κB activity and ubiquitin-like modifiers
Lang, V., & Rodríguez, M. S. (2008) · Biochemical Society Transactions · doi:10.1042/bst0360853 · Cited by 17 · see citing works
FKBP51 protects 661w cell culture from staurosporine-induced apoptosis.
Daudt, D. R., & Yorio, T. (2011) · PubMed Central · Cited by 15 · see citing works
NF-κB and Therapeutic Approach
Lee, C., & Kim, S. (2009) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2009.17.3.219 · Cited by 14 · see citing works
Powell, S. R. (2006) · Circulation Research · doi:10.1161/01.res.0000239412.40685.61 · Cited by 14 · see citing works
Role of Inflammation in the Development of COVID-19 to Parkinson’s Disease
Liu, T., Wu, H., Sun, L., & Wei, J. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s460161 · Cited by 12 · see citing works
Ubiquitination in host immune response to human papillomavirus infection
Zhou, Q., Zhu, K., & Cheng, H. (2011) · Archives of Dermatological Research · doi:10.1007/s00403-011-1141-0 · Cited by 12 · see citing works
Skvortsov, S., Skvortsova, I., Stasyk, T., Schiefermeier-Mach, N., Neher, A., Gunkel, A. R., Bonn, G. K., Huber, L. A., Lukas, P. H., Pleiman, C. M., et al. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0708 · Cited by 12 · see citing works
Sun, L., Pappy, A. L., Pham, T., & Shanley, T. P. (2015) · Biomolecules · doi:10.3390/biom5031284 · Cited by 10 · see citing works
Helicobacter pylori regulates TIFA turnover in gastric epithelial cells.
Sokolova, O. V., Maubach, G., & Naumann, M. (2023) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2023.151307 · Cited by 9 · see citing works
Proteasome inhibition in hypertrophied myocardium
Friehs, I. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00886.2008 · Cited by 9 · see citing works
Wu, F., Chen, Y., Chen, X., Tong, D., Zhou, J., Du, Z., Yao, C., Yang, Y., Du, A., & Ma, G. (2025) · Communications Biology · doi:10.1038/s42003-025-07803-8 · Cited by 6 · see citing works
Wang, P., Calise, J., Powell, K., Divald, A., & Powell, S. R. (2014) · Europe PMC (PubMed Central) · Cited by 5 · see citing works
Lee, J., Choi, K., & Choi, C. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.10.155 · Cited by 5 · see citing works
Smads keep TABs on inflammation
Seth, R. B., & Chen, Z. J. (2007) · Nature Immunology · doi:10.1038/ni0507-477 · Cited by 5 · see citing works
Effects of multi-walled carbon nanotubes on message and Micro-RNA in human lung BEAS-2B cells
Thai, S., Jones, C. P., Robinette, B. L., Nelson, G. B., Tennant, A. H., Ren, H., Vallanat, B., Fisher, A., Ross, J. A., & Kitchin, K. T. (2024) · Materials Express · doi:10.1166/mex.2024.2620 · Cited by 3 · see citing works
Ubiquitin‐Independent Mechanisms of Substrate Recognition and Degradation by the Proteasome
Hoyt, M. A., & Coffino, P. (2007) · Wiley eBooks · doi:10.1002/9783527619320.ch5c · Cited by 3 · see citing works
Ubiquitin Signaling and Cancer Pathogenesis
Haglund, K., & Đikić, I. (2007) · Wiley eBooks · doi:10.1002/9783527620234.ch1 · Cited by 2 · see citing works
- Authors
- Krappmann, D., & Scheidereit, C.
- Affiliations
- Max Delbrück Center (DE)
- Corresponding author
- Scheidereit, Claus
- Venue
- The EMBO Reports
- Published
- 2005-04-01
- Volume
- 6
- Issue
- 4
- Pages
- 321-326
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC1299290
- OpenAlex
- W2169463874
- Cited by
- 128
- References
- 41
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 2 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 6 · 2013: 5 · 2012: 5
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- EMBO Reports (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- ubiquitin conjugation, NF-κB signaling, IκB kinase, IκB degradation, Lys63-linked polyubiquitination, E3 ubiquitin ligase, deubiquitinase, c-Jun N-terminal kinase, 26S proteasome, signal termination
- MeSH terms
- Enzyme Activation, Gene Expression Regulation, Humans, Models, Biological, Signal Transduction, NF-kappa B, Protein Serine-Threonine Kinases, Ubiquitin, I-kappa B Kinase
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