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Sci. STKE, 17 October 2006
Vol. 2006, Issue 357, p. re13
[DOI: 10.1126/stke.3572006re13]


Regulation and Function of IKK and IKK-Related Kinases

Hans Häcker1* and Michael Karin2

1Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA.
2Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.

Gloss: With six figures and 199 references, this review describes the functions of and regulatory mechanisms controlling the activity of a family of kinases that are instrumental for activation of the host defense system. These kinases are called IKK and IKK-related kinases. The family includes IKK{alpha}, IKKbeta, and IKK{gamma}, which regulate the activity of the nuclear factor kappa B (NF-{kappa}B) family of dimeric transcription factors, and IKK{varepsilon} or IKK-i and one variously named TBK1 (TANK-binding kinase), NAK (NF-{kappa}B–activated kinase), or T2K (TRAF2-associated kinase), which regulate the activity of transcription factors that are important for the induction of type I interferon (IFN-I). Through an evaluation of the mechanisms by which NF-{kappa}b activity is regulated and the roles that each kinase plays in this process, as well as functions beyond NF-{kappa}B regulation, the authors provide insight into the roles these IKKs and related kinases play in immune responses, cell survival, and cancer.

*Corresponding author. E-mail, hans.haecker{at}

Citation: H. Häcker, M. Karin, Regulation and Function of IKK and IKK-Related Kinases. Sci. STKE 2006, re13 (2006).

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Lysine 63-linked Polyubiquitination of TAK1 at Lysine 158 Is Required for Tumor Necrosis Factor {alpha}- and Interleukin-1{beta}-induced IKK/NF-{kappa}B and JNK/AP-1 Activation.
Y. Fan, Y. Yu, Y. Shi, W. Sun, M. Xie, N. Ge, R. Mao, A. Chang, G. Xu, M. D. Schneider, et al. (2010)
J. Biol. Chem. 285, 5347-5360
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The Alpha/Beta Interferon Receptor Provides Protection against Influenza Virus Replication but Is Dispensable for Inflammatory Response Signaling.
A. G. Goodman, H. Zeng, S. C. Proll, X. Peng, C. Cilloniz, V. S. Carter, M. J. Korth, T. M. Tumpey, and M. G. Katze (2010)
J. Virol. 84, 2027-2037
   Abstract »    Full Text »    PDF »
The IKK complex contributes to the induction of autophagy.
A. Criollo, L. Senovilla, H. Authier, M. C. Maiuri, E. Morselli, I. Vitale, O. Kepp, E. Tasdemir, L. Galluzzi, S. Shen, et al. (2010)
EMBO J. 29, 619-631
   Abstract »    Full Text »    PDF »
Antioxidant Amelioration of Dilated Cardiomyopathy Caused by Conditional Deletion of NEMO/IKK{gamma} in Cardiomyocytes.
P. Kratsios, M. Huth, L. Temmerman, E. Salimova, M. Al Banchaabouchi, A. Sgoifo, M. Manghi, K. Suzuki, N. Rosenthal, and F. Mourkioti (2010)
Circ. Res. 106, 133-144
   Abstract »    Full Text »    PDF »
NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domain.
E. Laplantine, E. Fontan, J. Chiaravalli, T. Lopez, G. Lakisic, M. Veron, F. Agou, and A. Israel (2009)
EMBO J. 28, 2885-2895
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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 »
Specification of DNA Binding Activity of NF-{kappa}B Proteins.
F. Wan and M. J. Lenardo (2009)
Cold Spring Harb Perspect Biol 1, a000067
   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 »
Bcl3 Interacts Cooperatively with Peroxisome Proliferator-Activated Receptor Gamma (PPAR{gamma}) Coactivator 1{alpha} To Coactivate Nuclear Receptors Estrogen-Related Receptor {alpha} and PPAR{alpha}.
J. Yang, R. S. Williams, and D. P. Kelly (2009)
Mol. Cell. Biol. 29, 4091-4102
   Abstract »    Full Text »    PDF »
Linear polyubiquitination: a new regulator of NF-{kappa}B activation.
K. Iwai and F. Tokunaga (2009)
EMBO Rep. 10, 706-713
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Site-Specific Antiatherogenic Effect of the Antioxidant Ebselen in the Diabetic Apolipoprotein E-Deficient Mouse.
P. Chew, D. Y.C. Yuen, P. Koh, N. Stefanovic, M. A. Febbraio, I. Kola, M. E. Cooper, and J. B. de Haan (2009)
Arterioscler Thromb Vasc Biol 29, 823-830
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Synergistic Growth Inhibition of Squamous Cell Carcinoma of the Head and Neck by Erlotinib and Epigallocatechin-3-Gallate: The Role of p53-Dependent Inhibition of Nuclear Factor-{kappa}B.
A. R. M. R. Amin, F. R. Khuri, Z. Chen, and D. M. Shin (2009)
Cancer Prevention Research 2, 538-545
   Abstract »    Full Text »    PDF »
KiSS1 Metastasis Suppressor Gene Product Induces Suppression of Tyrosine Kinase Receptor Signaling to Akt, Tumor Necrosis Factor Family Ligand Expression, and Apoptosis.
J.-M. Navenot, N. Fujii, and S. C. Peiper (2009)
Mol. Pharmacol. 75, 1074-1083
   Abstract »    Full Text »    PDF »

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