Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 289 (5484): 1550-1554

Copyright © 2000 by the American Association for the Advancement of Science

Selective Inhibition of NF-kappa B Activation by a Peptide That Blocks the Interaction of NEMO with the Ikappa B Kinase Complex

Michael J. May,1 Fulvio D'Acquisto,1 Lisa A. Madge,2 Judith Glöckner,1 Jordan S. Pober,2 Sankar Ghosh1*

Activation of the transcription factor nuclear factor (NF)-kappa B by proinflammatory stimuli leads to increased expression of genes involved in inflammation. Activation of NF-kappa B requires the activity of an inhibitor of kappa B (Ikappa B)-kinase (IKK) complex containing two kinases (IKKalpha and IKKbeta ) and the regulatory protein NEMO (NF-kappa B essential modifier). An amino-terminal alpha -helical region of NEMO associated with a carboxyl-terminal segment of IKKalpha and IKKbeta that we term the NEMO-binding domain (NBD). A cell-permeable NBD peptide blocked association of NEMO with the IKK complex and inhibited cytokine-induced NF-kappa B activation and NF-kappa B-dependent gene expression. The peptide also ameliorated inflammatory responses in two experimental mouse models of acute inflammation. The NBD provides a target for the development of drugs that would block proinflammatory activation of the IKK complex without inhibiting basal NF-kappa B activity.

1 Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
2 Interdepartmental Program in Vascular Biology and Transplantation, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536, USA.
*   To whom correspondence should be addressed. E-mail: sankar.ghosh{at}

NF-{kappa}B Activation-Induced Anti-apoptosis Renders HER2-Positive Cells Drug Resistant and Accelerates Tumor Growth.
S. T. Bailey, P. L. Miron, Y. J. Choi, B. Kochupurakkal, G. Maulik, S. J. Rodig, R. Tian, K. M. Foley, T. Bowman, A. Miron, et al. (2014)
Mol. Cancer Res. 12, 408-420
   Abstract »    Full Text »    PDF »
Generation of an efficiently secreted, cell penetrating NF-{kappa}B inhibitor.
A. Koutsokeras, N. Purkayastha, A. Rigby, M. C. Subang, M. Sclanders, S. Vessillier, L. Mullen, Y. Chernajovsky, and D. Gould (2014)
FASEB J 28, 373-381
   Abstract »    Full Text »    PDF »
Toll-Like Receptor-2 Mediates Adaptive Cardiac Hypertrophy in Response to Pressure Overload Through Interleukin-1{beta} Upregulation via Nuclear Factor {kappa}B Activation.
Y. Higashikuni, K. Tanaka, M. Kato, O. Nureki, Y. Hirata, R. Nagai, I. Komuro, and M. Sata (2013)
JAHA 2, e000267
   Abstract »    Full Text »    PDF »
NF-{kappa}B inhibitor targeted to activated endothelium demonstrates a critical role of endothelial NF-{kappa}B in immune-mediated diseases.
B. Sehnert, H. Burkhardt, J. T. Wessels, A. Schroder, M. J. May, D. Vestweber, J. Zwerina, K. Warnatz, F. Nimmerjahn, G. Schett, et al. (2013)
PNAS 110, 16556-16561
   Abstract »    Full Text »    PDF »
A critical role of astrocyte-mediated nuclear factor-{kappa}B-dependent inflammation in Huntington's disease.
H.-Y. Hsiao, Y.-C. Chen, H.-M. Chen, P.-H. Tu, and Y. Chern (2013)
Hum. Mol. Genet. 22, 1826-1842
   Abstract »    Full Text »    PDF »
Novel Phosphorylations of IKK{gamma}/NEMO.
S. H. Lee, Z. Toth, L.-Y. Wong, K. Brulois, J. Nguyen, J.-Y. Lee, E. Zandi, and J. U. Jung (2012)
mBio 3, e00411-12
   Abstract »    Full Text »    PDF »
Activation of the noncanonical NF-{kappa}B pathway by HIV controls a dendritic cell immunoregulatory phenotype.
O. Manches, M. V. Fernandez, J. Plumas, L. Chaperot, and N. Bhardwaj (2012)
PNAS 109, 14122-14127
   Abstract »    Full Text »    PDF »
Structural Insights into the Assembly of Large Oligomeric Signalosomes in the Toll-Like Receptor-Interleukin-1 Receptor Superfamily.
R. Ferrao, J. Li, E. Bergamin, and H. Wu (2012)
Science Signaling 5, re3
   Abstract »    Full Text »    PDF »
The MC159 Protein from the Molluscum Contagiosum Poxvirus Inhibits NF-{kappa}B Activation by Interacting with the I{kappa}B Kinase Complex.
C. M. H. Randall, J. A. Jokela, and J. L. Shisler (2012)
J. Immunol. 188, 2371-2379
   Abstract »    Full Text »    PDF »
Control of Type I Interferon-induced Cell Death by Orai1-mediated Calcium Entry in T Cells.
C. Yue, J. Soboloff, and A. M. Gamero (2012)
J. Biol. Chem. 287, 3207-3216
   Abstract »    Full Text »    PDF »
Disruption of I{kappa}B Kinase (IKK)-mediated RelA Serine 536 Phosphorylation Sensitizes Human Multiple Myeloma Cells to Histone Deacetylase (HDAC) Inhibitors.
Y. Dai, S. Chen, L. Wang, X.-Y. Pei, V. L. Funk, L. B. Kramer, P. Dent, and S. Grant (2011)
J. Biol. Chem. 286, 34036-34050
   Abstract »    Full Text »    PDF »
NF-{kappa}B Signaling Participates in Both RANKL- and IL-4-Induced Macrophage Fusion: Receptor Cross-Talk Leads to Alterations in NF-{kappa}B Pathways.
M. Yu, X. Qi, J. L. Moreno, D. L. Farber, and A. D. Keegan (2011)
J. Immunol. 187, 1797-1806
   Abstract »    Full Text »    PDF »
NEMO-Binding Domain Peptide Inhibits Constitutive NF-{kappa}B Activity and Reduces Tumor Burden in a Canine Model of Relapsed, Refractory Diffuse Large B-Cell Lymphoma.
A. Gaurnier-Hausser, R. Patel, A. S. Baldwin, M. J. May, and N. J. Mason (2011)
Clin. Cancer Res. 17, 4661-4671
   Abstract »    Full Text »    PDF »
Protection from diabetes development by single-chain antibody-mediated delivery of a NF-{kappa}B inhibitor specifically to {beta}-cells in vivo.
S. Ueberberg, T. Deutschbein, H. H. Klein, J. W. Dietrich, S. Akinturk, N. Prochnow, R. Schirrmacher, and S. Schneider (2011)
Am J Physiol Endocrinol Metab 301, E83-E90
   Abstract »    Full Text »    PDF »
The Measles Virus V Protein Binds to p65 (RelA) To Suppress NF-{kappa}B Activity.
K. M. Schuhmann, C. K. Pfaller, and K.-K. Conzelmann (2011)
J. Virol. 85, 3162-3171
   Abstract »    Full Text »    PDF »
TNF{alpha}-induced noncanonical NF-{kappa}B activation is attenuated by RIP1 through stabilization of TRAF2.
J.-Y. Kim, M. Morgan, D.-G. Kim, J.-Y. Lee, L. Bai, Y. Lin, Z.-g. Liu, and Y.-S. Kim (2011)
J. Cell Sci. 124, 647-656
   Abstract »    Full Text »    PDF »
The Apolipoprotein E-Mimetic Peptide COG112 Inhibits NF-{kappa}B Signaling, Proinflammatory Cytokine Expression, and Disease Activity in Murine Models of Colitis.
K. Singh, R. Chaturvedi, D. P. Barry, L. A. Coburn, M. Asim, N. D. Lewis, M. B. Piazuelo, M. K. Washington, M. P. Vitek, and K. T. Wilson (2011)
J. Biol. Chem. 286, 3839-3850
   Abstract »    Full Text »    PDF »
The I{kappa}B Kinase Inhibitor Nuclear Factor-{kappa}B Essential Modulator-Binding Domain Peptide for Inhibition of Injury-Induced Neointimal Formation.
G. Grassia, M. Maddaluno, C. Musilli, D. De Stefano, R. Carnuccio, M. V. Di Lauro, C. A. Parratt, S. Kennedy, P. Di Meglio, A. Ianaro, et al. (2010)
Arterioscler Thromb Vasc Biol 30, 2458-2466
   Abstract »    Full Text »    PDF »
Chromosome 1 Open Reading Frame 190 Promotes Activation of NF-{kappa}B Canonical Pathway and Resistance of Dendritic Cells to Tumor-Associated Inhibition In Vitro.
Z. Jing, X. Yuan, J. Zhang, X. Huang, Z. Zhang, J. Liu, M. Zhang, J. Oyang, Y. Zhang, Z. Zhang, et al. (2010)
J. Immunol. 185, 6719-6727
   Abstract »    Full Text »    PDF »
NF{kappa}B activation and stimulation of chemokine production in normal human macrophages by the gadolinium-based magnetic resonance contrast agent Omniscan: possible role in the pathogenesis of nephrogenic systemic fibrosis.
F. D. Galdo, P. J. Wermuth, S. Addya, P. Fortina, and S. A. Jimenez (2010)
Ann Rheum Dis 69, 2024-2033
   Abstract »    Full Text »    PDF »
Roles of Bcl-3 in the Pathogenesis of Murine Type 1 Diabetes.
Q. Ruan, S.-J. Zheng, S. Palmer, R. J. Carmody, and Y. H. Chen (2010)
Diabetes 59, 2549-2557
   Abstract »    Full Text »    PDF »
Muc1 Cell Surface Mucin Attenuates Epithelial Inflammation in Response to a Common Mucosal Pathogen.
W. Guang, H. Ding, S. J. Czinn, K. C. Kim, T. G. Blanchard, and E. P. Lillehoj (2010)
J. Biol. Chem. 285, 20547-20557
   Abstract »    Full Text »    PDF »
A newly identified bacterial cell-penetrating peptide that reduces the transcription of pro-inflammatory cytokines.
C. Ruter, C. Buss, J. Scharnert, G. Heusipp, and M. A. Schmidt (2010)
J. Cell Sci. 123, 2190-2198
   Abstract »    Full Text »    PDF »
Expression of Type III Interferon (IFN) in the Vaginal Mucosa Is Mediated Primarily by Dendritic Cells and Displays Stronger Dependence on NF-{kappa}B than Type I IFNs.
M. B. Iversen, N. Ank, J. Melchjorsen, and S. R. Paludan (2010)
J. Virol. 84, 4579-4586
   Abstract »    Full Text »    PDF »
Novel Insights into the Cellular Mechanisms of the Anti-inflammatory Effects of NF-{kappa}B Essential Modulator Binding Domain Peptides.
E. T. Baima, J. A. Guzova, S. Mathialagan, E. E. Nagiec, M. M. Hardy, L. R. Song, S. L. Bonar, R. A. Weinberg, S. R. Selness, S. S. Woodard, et al. (2010)
J. Biol. Chem. 285, 13498-13506
   Abstract »    Full Text »    PDF »
NF-{kappa}B Signaling: A Tale of Two Pathways in Skeletal Myogenesis.
N. Bakkar and D. C. Guttridge (2010)
Physiol Rev 90, 495-511
   Abstract »    Full Text »    PDF »
Ca2+ influx via TRPC channels induces NF-{kappa}B-dependent A20 expression to prevent thrombin-induced apoptosis in endothelial cells.
P. B. Thippegowda, V. Singh, P. C. Sundivakkam, J. Xue, A. B. Malik, and C. Tiruppathi (2010)
Am J Physiol Cell Physiol 298, C656-C664
   Abstract »    Full Text »    PDF »
The IKK Complex, a Central Regulator of NF-{kappa}B Activation.
A. Israel (2010)
Cold Spring Harb Perspect Biol 2, a000158
   Abstract »    Full Text »    PDF »
Regulation of p53 Family Member Isoform {Delta}Np63{alpha} by the Nuclear Factor-{kappa}B Targeting Kinase I{kappa}B Kinase {beta}.
A. Chatterjee, X. Chang, T. Sen, R. Ravi, A. Bedi, and D. Sidransky (2010)
Cancer Res. 70, 1419-1429
   Abstract »    Full Text »    PDF »
20-Hydroxy-5,8,11,14-eicosatetraenoic Acid Mediates Endothelial Dysfunction via I{kappa}B Kinase-Dependent Endothelial Nitric-Oxide Synthase Uncoupling.
J. Cheng, C.-C. Wu, K. H. Gotlinger, F. Zhang, J. R. Falck, D. Narsimhaswamy, and M. L. Schwartzman (2010)
J. Pharmacol. Exp. Ther. 332, 57-65
   Abstract »    Full Text »    PDF »
Hemorrhagic shock augments lung endothelial cell activation: role of temporal alterations of TLR4 and TLR2.
Y. Li, M. Xiang, Y. Yuan, G. Xiao, J. Zhang, Y. Jiang, Y. Vodovotz, T. R. Billiar, M. A. Wilson, and J. Fan (2009)
Am J Physiol Regulatory Integrative Comp Physiol 297, R1670-R1680
   Abstract »    Full Text »    PDF »
NEMO-binding Domains of Both IKK{alpha} and IKK{beta} Regulate I{kappa}B Kinase Complex Assembly and Classical NF-{kappa}B Activation.
L. A. Solt, L. A. Madge, and M. J. May (2009)
J. Biol. Chem. 284, 27596-27608
   Abstract »    Full Text »    PDF »
The NF-{kappa}B Family of Transcription Factors and Its Regulation.
A. Oeckinghaus and S. Ghosh (2009)
Cold Spring Harb Perspect Biol 1, a000034
   Abstract »    Full Text »    PDF »
Functional Cross-talk between {beta}-Catenin and NF{kappa}B Signaling Pathways in Colonic Crypts of Mice in Response to Progastrin.
S. Umar, S. Sarkar, Y. Wang, and P. Singh (2009)
J. Biol. Chem. 284, 22274-22284
   Abstract »    Full Text »    PDF »
TNF-{alpha} Preconditioning Protects Neurons via Neuron-Specific Up-Regulation of CREB-Binding Protein.
R. N. Saha, A. Ghosh, C. A. Palencia, Y. K. Fung, S. M. Dudek, and K. Pahan (2009)
J. Immunol. 183, 2068-2078
   Abstract »    Full Text »    PDF »
Matrix metalloproteinase-9 inhibition ameliorates pathogenesis and improves skeletal muscle regeneration in muscular dystrophy.
H. Li, A. Mittal, D. Y. Makonchuk, S. Bhatnagar, and A. Kumar (2009)
Hum. Mol. Genet. 18, 2584-2598
   Abstract »    Full Text »    PDF »
Constitutive NF-{kappa}B Activation in Colorectal Carcinoma Plays a Key Role in Angiogenesis, Promoting Tumor Growth.
K. Sakamoto, S. Maeda, Y. Hikiba, H. Nakagawa, Y. Hayakawa, W. Shibata, A. Yanai, K. Ogura, and M. Omata (2009)
Clin. Cancer Res. 15, 2248-2258
   Abstract »    Full Text »    PDF »
The Orphan Nuclear Receptor Nur77 Suppresses Endothelial Cell Activation Through Induction of I{kappa}B{alpha} Expression.
B. You, Y.-Y. Jiang, S. Chen, G. Yan, and J. Sun (2009)
Circ. Res. 104, 742-749
   Abstract »    Full Text »    PDF »
Chitin Is a Size-Dependent Regulator of Macrophage TNF and IL-10 Production.
C. A. Da Silva, C. Chalouni, A. Williams, D. Hartl, C. G. Lee, and J. A. Elias (2009)
J. Immunol. 182, 3573-3582
   Abstract »    Full Text »    PDF »
Developmental regulation of MHC II expression and transport in human plasmacytoid-derived dendritic cells.
C. Sadaka, M.-A. Marloie-Provost, V. Soumelis, and P. Benaroch (2009)
Blood 113, 2127-2135
   Abstract »    Full Text »    PDF »
Ca2+ Entry via TRPC Channels Is Necessary for Thrombin-induced NF-{kappa}B Activation in Endothelial Cells through AMP-activated Protein Kinase and Protein Kinase C{delta}.
A. M. Bair, P. B. Thippegowda, M. Freichel, N. Cheng, R. D. Ye, S. M. Vogel, Y. Yu, V. Flockerzi, A. B. Malik, and C. Tiruppathi (2009)
J. Biol. Chem. 284, 563-574
   Abstract »    Full Text »    PDF »
Compensatory IKK{alpha} activation of classical NF-{kappa}B signaling during IKK{beta} inhibition identified by an RNA interference sensitization screen.
L. T. Lam, R. E. Davis, V. N. Ngo, G. Lenz, G. Wright, W. Xu, H. Zhao, X. Yu, L. Dang, and L. M. Staudt (2008)
PNAS 105, 20798-20803
   Abstract »    Full Text »    PDF »
Regulation of I{kappa}B Kinase Complex by Phosphorylation of {gamma}-Binding Domain of I{kappa}B Kinase {beta} by Polo-like Kinase 1.
T. Higashimoto, N. Chan, Y.-K. Lee, and E. Zandi (2008)
J. Biol. Chem. 283, 35354-35367
   Abstract »    Full Text »    PDF »
Advances in Targeting IKK and IKK-Related Kinases for Cancer Therapy.
D.-F. Lee and M.-C. Hung (2008)
Clin. Cancer Res. 14, 5656-5662
   Abstract »    Full Text »    PDF »
A Dual Role of the NF-{kappa}B Pathway in Neonatal Hypoxic-Ischemic Brain Damage.
C. H. Nijboer, C. J. Heijnen, F. Groenendaal, M. J. May, F. van Bel, and A. Kavelaars (2008)
Stroke 39, 2578-2586
   Abstract »    Full Text »    PDF »
Strong Neuroprotection by Inhibition of NF-{kappa}B After Neonatal Hypoxia-Ischemia Involves Apoptotic Mechanisms but Is Independent of Cytokines.
C. H.A. Nijboer, C. J. Heijnen, F. Groenendaal, M. J. May, F. van Bel, and A. Kavelaars (2008)
Stroke 39, 2129-2137
   Abstract »    Full Text »    PDF »
Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-{kappa}B activation.
H. Iha, J.-M. Peloponese, L. Verstrepen, G. Zapart, F. Ikeda, C. D. Smith, M. F. Starost, V. Yedavalli, K. Heyninck, I. Dikic, et al. (2008)
EMBO J. 27, 629-641
   Abstract »    Full Text »    PDF »
Role of NF-{kappa}B-dependent Caveolin-1 Expression in the Mechanism of Increased Endothelial Permeability Induced by Lipopolysaccharide.
C. Tiruppathi, J. Shimizu, K. Miyawaki-Shimizu, S. M. Vogel, A. M. Bair, R. D. Minshall, D. Predescu, and A. B. Malik (2008)
J. Biol. Chem. 283, 4210-4218
   Abstract »    Full Text »    PDF »
Nuclear Factor-{kappa}B Activation: From Bench to Bedside.
G. Sethi, B. Sung, and B. B. Aggarwal (2008)
Experimental Biology and Medicine 233, 21-31
   Abstract »    Full Text »    PDF »
Selective inhibition of NF-{kappa}B activation prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease.
A. Ghosh, A. Roy, X. Liu, J. H. Kordower, E. J. Mufson, D. M. Hartley, S. Ghosh, R. L. Mosley, H. E. Gendelman, and K. Pahan (2007)
PNAS 104, 18754-18759
   Abstract »    Full Text »    PDF »
Inhibition of NF-{kappa}B Activation Reduces the Tissue Effects of Transgenic IL-13.
S. P. Chapoval, A. Al-Garawi, J. M. Lora, I. Strickland, B. Ma, P. J. Lee, R. J. Homer, S. Ghosh, A. J. Coyle, and J. A. Elias (2007)
J. Immunol. 179, 7030-7041
   Abstract »    Full Text »    PDF »
Moraxella catarrhalis induces ERK- and NF-{kappa}B-dependent COX-2 and prostaglandin E2 in lung epithelium.
P. D. N'Guessan, B. Temmesfeld-Wollbruck, J. Zahlten, J. Eitel, S. Zabel, B. Schmeck, B. Opitz, S. Hippenstiel, N. Suttorp, and H. Slevogt (2007)
Eur. Respir. J. 30, 443-451
   Abstract »    Full Text »    PDF »
Cutting Edge: The I{kappa}B Kinase (IKK) Inhibitor, NEMO-Binding Domain Peptide, Blocks Inflammatory Injury in Murine Colitis.
W. Shibata, S. Maeda, Y. Hikiba, A. Yanai, T. Ohmae, K. Sakamoto, H. Nakagawa, K. Ogura, and M. Omata (2007)
J. Immunol. 179, 2681-2685
   Abstract »    Full Text »    PDF »
Noncanonical NF-{kappa}B signaling in dendritic cells is required for indoleamine 2,3-dioxygenase (IDO) induction and immune regulation.
S. W. Tas, M. J. Vervoordeldonk, N. Hajji, J. H. N. Schuitemaker, K. F. van der Sluijs, M. J. May, S. Ghosh, M. L. Kapsenberg, P. P. Tak, and E. C. de Jong (2007)
Blood 110, 1540-1549
   Abstract »    Full Text »    PDF »
Inhibition of Experimental Allergic Airways Disease by Local Application of a Cell-Penetrating Dominant-Negative STAT-6 Peptide.
C. T. McCusker, Y. Wang, J. Shan, M. W. Kinyanjui, A. Villeneuve, H. Michael, and E. D. Fixman (2007)
J. Immunol. 179, 2556-2564
   Abstract »    Full Text »    PDF »
SINTBAD, a novel component of innate antiviral immunity, shares a TBK1-binding domain with NAP1 and TANK.
G. Ryzhakov and F. Randow (2007)
EMBO J. 26, 3180-3190
   Abstract »    Full Text »    PDF »
Vacuolating Cytotoxin in Helicobacter pylori Water-Soluble Proteins Upregulates Chemokine Expression in Human Eosinophils via Ca2+ Influx, Mitochondrial Reactive Oxygen Intermediates, and NF-{kappa}B Activation.
J. M. Kim, J. S. Kim, J. Y. Lee, Y.-J. Kim, H.-J. Youn, I. Y. Kim, Y. J. Chee, Y.-K. Oh, N. Kim, H. C. Jung, et al. (2007)
Infect. Immun. 75, 3373-3381
   Abstract »    Full Text »    PDF »
Nuclear factor-{kappa}B activation: a molecular therapeutic target for estrogen receptor-negative and epidermal growth factor receptor family receptor-positive human breast cancer.
S. Singh, Q. Shi, S. T. Bailey, M. J. Palczewski, A. B. Pardee, J. D. Iglehart, and D. K. Biswas (2007)
Mol. Cancer Ther. 6, 1973-1982
   Abstract »    Full Text »    PDF »
Ethanol induced NF-{kappa}B activation protects against cell injury in cultured rat gastric mucosal epithelium.
H. Mustonen, A. Hietaranta, P. Puolakkainen, E. Kemppainen, H. Paimela, T. Kiviluoto, and E. Kivilaakso (2007)
Am J Physiol Gastrointest Liver Physiol 292, G1614-G1621
   Abstract »    Full Text »    PDF »
NF-{kappa}B is important for TNF-{alpha}-induced lipolysis in human adipocytes.
J. Laurencikiene, V. van Harmelen, E. Arvidsson Nordstrom, A. Dicker, L. Blomqvist, E. Naslund, D. Langin, P. Arner, and M. Ryden (2007)
J. Lipid Res. 48, 1069-1077
   Abstract »    Full Text »    PDF »
Heptad Repeats Regulate Protein Phosphatase 2A Recruitment to I-{kappa}B Kinase {gamma}/NF-{kappa}B Essential Modulator and Are Targeted by Human T-lymphotropic Virus Type 1 Tax.
S. Hong, L.-C. Wang, X. Gao, Y.-L. Kuo, B. Liu, R. Merling, H.-J. Kung, H.-M. Shih, and C.-Z. Giam (2007)
J. Biol. Chem. 282, 12119-12126
   Abstract »    Full Text »    PDF »
Interleukin-1-induced NF-{kappa}B Activation Is NEMO-dependent but Does Not Require IKKbeta.
L. A. Solt, L. A. Madge, J. S. Orange, and M. J. May (2007)
J. Biol. Chem. 282, 8724-8733
   Abstract »    Full Text »    PDF »
B7-DC/PD-L2 Cross-Linking Induces NF-{kappa}B-Dependent Protection of Dendritic Cells from Cell Death.
S. Radhakrishnan, L. T. Nguyen, B. Ciric, V. P. Van Keulen, and L. R. Pease (2007)
J. Immunol. 178, 1426-1432
   Abstract »    Full Text »    PDF »
Legionella pneumophila-induced PKC{alpha}-, MAPK-, and NF-{kappa}B-dependent COX-2 expression in human lung epithelium.
P. D. N'Guessan, M. O. Etouem, B. Schmeck, A. C. Hocke, S. Scharf, K. Vardarova, B. Opitz, A. Flieger, N. Suttorp, and S. Hippenstiel (2007)
Am J Physiol Lung Cell Mol Physiol 292, L267-L277
   Abstract »    Full Text »    PDF »
Dimerization of the I{kappa}B Kinase-Binding Domain of NEMO Is Required for Tumor Necrosis Factor Alpha-Induced NF-{kappa}B Activity.
R. B. Marienfeld, L. Palkowitsch, and S. Ghosh (2006)
Mol. Cell. Biol. 26, 9209-9219
   Abstract »    Full Text »    PDF »
Review: Ubiquitination and de-ubiquitination: role in regulation of signaling by Toll-like receptors.
E. L. Lowe, T. M. Doherty, H. Karahashi, and M. Arditi (2006)
Innate Immunity 12, 337-345
   Abstract »    PDF »
Substance P treatment stimulates chemokine synthesis in pancreatic acinar cells via the activation of NF-{kappa}B.
R. D. Ramnath and M. Bhatia (2006)
Am J Physiol Gastrointest Liver Physiol 291, G1113-G1119
   Abstract »    Full Text »    PDF »
Transglutaminase 2 Mediates Polymer Formation of I-{kappa}B{alpha} through C-terminal Glutamine Cluster.
S.-S. Park, J.-M. Kim, D.-S. Kim, I.-H. Kim, and S.-Y. Kim (2006)
J. Biol. Chem. 281, 34965-34972
   Abstract »    Full Text »    PDF »
Id1 Potentiates NF-{kappa}B Activation upon T Cell Receptor Signaling.
Y. Yang, H.-C. Liou, and X.-H. Sun (2006)
J. Biol. Chem. 281, 34989-34996
   Abstract »    Full Text »    PDF »
Use of cell permeable NBD peptides for suppression of inflammation.
I Strickland and S Ghosh (2006)
Ann Rheum Dis 65, iii75-iii82
   Abstract »    Full Text »    PDF »
Regulation and Function of IKK and IKK-Related Kinases.
H. Hacker and M. Karin (2006)
Sci. STKE 2006, re13
   Abstract »    Full Text »    PDF »
A Dominant Function of IKK/NF-{kappa}B Signaling in Global Lipopolysaccharide-induced Gene Expression.
N. Carayol, J. Chen, F. Yang, T. Jin, L. Jin, D. States, and C.-Y. Wang (2006)
J. Biol. Chem. 281, 31142-31151
   Abstract »    Full Text »    PDF »
Ca2+ Influx Induced by Protease-activated Receptor-1 Activates a Feed-forward Mechanism of TRPC1 Expression via Nuclear Factor-{kappa}B Activation in Endothelial Cells.
B. C. Paria, A. M. Bair, J. Xue, Y. Yu, A. B. Malik, and C. Tiruppathi (2006)
J. Biol. Chem. 281, 20715-20727
   Abstract »    Full Text »    PDF »
AGRO100 inhibits activation of nuclear factor-{kappa}B (NF-{kappa}B) by forming a complex with NF-{kappa}B essential modulator (NEMO) and nucleolin..
A. C. Girvan, Y. Teng, L. K. Casson, S. D. Thomas, S. Juliger, M. W. Ball, J. B. Klein, W. M. Pierce Jr., S. S. Barve, and P. J. Bates (2006)
Mol. Cancer Ther. 5, 1790-1799
   Abstract »    Full Text »    PDF »
Regulation of I{kappa}B Kinase (IKK) Complex by IKK{gamma}-dependent Phosphorylation of the T-loop and C Terminus of IKKbeta.
B. Schomer-Miller, T. Higashimoto, Y.-K. Lee, and E. Zandi (2006)
J. Biol. Chem. 281, 15268-15276
   Abstract »    Full Text »    PDF »
Streptococcus pneumoniae induced p38 MAPK- and NF-{kappa}B-dependent COX-2 expression in human lung epithelium.
P. D. N'Guessan, S. Hippenstiel, M. O. Etouem, J. Zahlten, W. Beermann, D. Lindner, B. Opitz, M. Witzenrath, S. Rosseau, N. Suttorp, et al. (2006)
Am J Physiol Lung Cell Mol Physiol 290, L1131-L1138
   Abstract »    Full Text »    PDF »
Gene therapy as a therapeutic approach for the treatment of rheumatoid arthritis: innovative vectors and therapeutic genes.
J. Adriaansen, M. J. B. M. Vervoordeldonk, and P. P. Tak (2006)
Rheumatology 45, 656-668
   Abstract »    Full Text »    PDF »
Induction of glial fibrillary acidic protein expression in astrocytes by nitric oxide..
S. Brahmachari, Y. K. Fung, and K. Pahan (2006)
J. Neurosci. 26, 4930-4939
   Abstract »    Full Text »    PDF »
An Alternative Splice Product of I{kappa}B Kinase (IKK{gamma}), IKK{gamma}-{Delta}, Differentially Mediates Cytokine and Human T-Cell Leukemia Virus Type 1 Tax-Induced NF-{kappa}B Activation.
T. Hai, M.-L. Yeung, T. G. Wood, Y. Wei, S. Yamaoka, Z. Gatalica, K.-T. Jeang, and A. R. Brasier (2006)
J. Virol. 80, 4227-4241
   Abstract »    Full Text »    PDF »
NF-{kappa}B is dispensable for normal lymphocyte development in bone marrow but required for protection of progenitors from TNF{alpha}.
H. Igarashi, Y. Baba, Y. Nagai, E. Jimi, S. Ghosh, and P. W Kincade (2006)
Int. Immunol. 18, 653-659
   Abstract »    Full Text »    PDF »
Moraxella catarrhalis induces inflammatory response of bronchial epithelial cells via MAPK and NF-{kappa}B activation and histone deacetylase activity reduction.
H. Slevogt, B. Schmeck, C. Jonatat, J. Zahlten, W. Beermann, V. van Laak, B. Opitz, S. Dietel, P. D. N'Guessan, S. Hippenstiel, et al. (2006)
Am J Physiol Lung Cell Mol Physiol 290, L818-L826
   Abstract »    Full Text »    PDF »
A Point Mutation in NEMO Associated with Anhidrotic Ectodermal Dysplasia with Immunodeficiency Pathology Results in Destabilization of the Oligomer and Reduces Lipopolysaccharide- and Tumor Necrosis Factor-mediated NF-{kappa}B Activation.
E. Vinolo, H. Sebban, A. Chaffotte, A. Israel, G. Courtois, M. Veron, and F. Agou (2006)
J. Biol. Chem. 281, 6334-6348
   Abstract »    Full Text »    PDF »
Disruption of SLP-76 Interaction with Gads Inhibits Dynamic Clustering of SLP-76 and Fc{varepsilon}RI Signaling in Mast Cells.
M. A. Silverman, J. Shoag, J. Wu, and G. A. Koretzky (2006)
Mol. Cell. Biol. 26, 1826-1838
   Abstract »    Full Text »    PDF »
Transcription regulation from a TATA and INR-less promoter: spatial segregation of promoter function.
A. A. George, M. Sharma, B. N. Singh, N. C. Sahoo, and K. V. Rao (2006)
EMBO J. 25, 811-821
   Abstract »    Full Text »    PDF »
The Kinase Complex Responsible for IRF-3-Mediated IFN-{beta} Production in Myeloid Dendritic Cells (mDC).
M. Sasai, M. Matsumoto, and T. Seya (2006)
J. Biochem. 139, 171-175
   Abstract »    Full Text »    PDF »
Conjugated Linoleic Acid Promotes Human Adipocyte Insulin Resistance through NF{kappa}B-dependent Cytokine Production.
S. Chung, J. M. Brown, J. N. Provo, R. Hopkins, and M. K. McIntosh (2005)
J. Biol. Chem. 280, 38445-38456
   Abstract »    Full Text »    PDF »
Inhibition of Nuclear Translocation of Nuclear Factor-{kappa}B Despite Lack of Functional I{kappa}B{alpha} Protein Overcomes Multiple Defects in Apoptosis Signaling in Human B-Cell Malignancies.
R. K. Thomas, M. L. Sos, T. Zander, O. Mani, A. Popov, D. Berenbrinker, S. Smola-Hess, J. L. Schultze, and J. Wolf (2005)
Clin. Cancer Res. 11, 8186-8194
   Abstract »    Full Text »    PDF »
Positive Regulation of I{kappa}B Kinase Signaling by Protein Serine/Threonine Phosphatase 2A.
A. E. Kray, R. S. Carter, K. N. Pennington, R. J. Gomez, L. E. Sanders, J. M. Llanes, W. N. Khan, D. W. Ballard, and B. E. Wadzinski (2005)
J. Biol. Chem. 280, 35974-35982
   Abstract »    Full Text »    PDF »
Prevention of NF-{kappa}B activation in vivo by a cell-permeable NF-{kappa}B inhibitor peptide.
A. L. Mora, J. LaVoy, M. McKean, A. Stecenko, K. L. Brigham, R. Parker, and M. Rojas (2005)
Am J Physiol Lung Cell Mol Physiol 289, L536-L544
   Abstract »    Full Text »    PDF »
Bcl10 can promote survival of antigen-stimulated B lymphocytes.
M. T. Tian, G. Gonzalez, B. Scheer, and A. L. DeFranco (2005)
Blood 106, 2105-2112
   Abstract »    Full Text »    PDF »
Cationic cell-penetrating peptides interfere with TNF signalling by induction of TNF receptor internalization.
M. Fotin-Mleczek, S. Welte, O. Mader, F. Duchardt, R. Fischer, H. Hufnagel, P. Scheurich, and R. Brock (2005)
J. Cell Sci. 118, 3339-3351
   Abstract »    Full Text »    PDF »
NF-{kappa}B inhibition radiosensitizes Ki-Ras-transformed cells to ionizing radiation.
B. Y. Kim, K. A. Kim, O. Kwon, S. O. Kim, M. S. Kim, B. S. Kim, W. K. Oh, G. D. Kim, M. Jung, and J. S. Ahn (2005)
Carcinogenesis 26, 1395-1403
   Abstract »    Full Text »    PDF »
Identification of Direct Genomic Targets Downstream of the Nuclear Factor-{kappa}B Transcription Factor Mediating Tumor Necrosis Factor Signaling.
B. Tian, D. E. Nowak, M. Jamaluddin, S. Wang, and A. R. Brasier (2005)
J. Biol. Chem. 280, 17435-17448
   Abstract »    Full Text »    PDF »
Nuclear Factor-{kappa}B-Dependent Mechanisms in Breast Cancer Cells Regulate Tumor Burden and Osteolysis in Bone.
A. H. Gordon, R. J. O'Keefe, E. M. Schwarz, R. N. Rosier, and J. E. Puzas (2005)
Cancer Res. 65, 3209-3217
   Abstract »    Full Text »    PDF »
PDK1 Nucleates T Cell Receptor-Induced Signaling Complex for NF-{kappa}B Activation.
K.-Y. Lee, F. D'Acquisto, M. S. Hayden, J.-H. Shim, and S. Ghosh (2005)
Science 308, 114-118
   Abstract »    Full Text »    PDF »
The nuclear factor {kappa}B inhibitor parthenolide restores ICI 182,780 (Faslodex; fulvestrant)-induced apoptosis in antiestrogen-resistant breast cancer cells.
R. B. Riggins, A. Zwart, R. Nehra, and R. Clarke (2005)
Mol. Cancer Ther. 4, 33-41
   Abstract »    Full Text »    PDF »
Inhibition of NF-{kappa}B Activation by Peptides Targeting NF-{kappa}B Essential Modulator (NEMO) Oligomerization.
F. Agou, G. Courtois, J. Chiaravalli, F. Baleux, Y.-M. Coic, F. Traincard, A. Israel, and M. Veron (2004)
J. Biol. Chem. 279, 54248-54257
   Abstract »    Full Text »    PDF »
Streptococcus pneumoniae-induced p38 MAPK-dependent Phosphorylation of RelA at the Interleukin-8 Promotor.
B. Schmeck, J. Zahlten, K. Moog, V. van Laak, S. Huber, A. C. Hocke, B. Opitz, E. Hoffmann, M. Kracht, J. Zerrahn, et al. (2004)
J. Biol. Chem. 279, 53241-53247
   Abstract »    Full Text »    PDF »
ATP-binding Cassette Transporter A1 Contains a Novel C-terminal VFVNFA Motif That Is Required for Its Cholesterol Efflux and ApoA-I Binding Activities.
M. L. Fitzgerald, K.-i. Okuhira, G. F. Short III, J. J. Manning, S. A. Bell, and M. W. Freeman (2004)
J. Biol. Chem. 279, 48477-48485
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882