IKAP is a scaffold protein of the IκB kinase complex

@article{Cohen1998IKAPIA,
  title={IKAP is a scaffold protein of the I$\kappa$B kinase complex},
  author={Lucie Cohen and William J. Henzel and Patrick A. Baeuerle},
  journal={Nature},
  year={1998},
  volume={395},
  pages={292-296}
}
The transcription factor NF-κB coordinates the activation of numerous genes in response to pathogens and pro-inflammatory cytokines, and is, therefore, vital in the development of acute and chronic inflammatory diseases. NF-κB is activated by phsophorylation of its inhibitory subunit, IκB-α (ref. 7), on serine residues 32 and 36 by cytokine-activated IκB kinases (IKKs); this phosphorylation precedes rapid degradation of IκB. IKK-α and IKK-β isozymes are found in large complexes of relative… 
The IκB kinase (IKK) and NF-κB: key elements of proinflammatory signalling
TLDR
There is strong biochemical and genetic evidence that the IKK complex, which consists of two catalytic subunits, IKKα and IKKβ, and a regulatory subunit, Ikkγ, is the master regulator of NF-κB-mediated innate immune and inflammatory responses.
How NF-κB is activated: the role of the IκB kinase (IKK) complex
TLDR
This review describes the identification of proteins in the IKK complex, and the regulation and physiological functions of IKK.
The IкB Kinase (IKK) Complex
TLDR
The activation of the IKK complex is the critical step in NF-кB signaling and therefore the regulation and function of this pathway are tightly linked to the subunits of IKK.
Activation of the IκB Kinases by RIP via IKKγ/NEMO-mediated Oligomerization*
TLDR
Gel filtration analysis of the IKK complex revealed that TNFα stimulation induces a large increase in the size of this complex, suggesting oligomerization, and data suggest that IKKγ functions as a signaling adaptor between the upstream regulators such as RIP and the Ikks and that oligomersization of theIKK complex by upstream regulators is a critical step in activation of thiscomplex.
The NF-κB Activation Pathway: A Paradigm in Information Transfer from Membrane to Nucleus
TLDR
Exposure of cells to various extracellular stimuli leads to the rapid phosphorylation, ubiquitinylation, and ultimately proteolytic degradation of IκB, which frees NF-κB to translocate to the nucleus, where it regulates gene transcription.
Identification of the receptor component of the IκBα–ubiquitin ligase
TLDR
The specific component of the ligase that recognizes the pIκBα degradation motif as an F-box/WD-domainprotein belonging to a recently distinguished family of β-TrCP/Slimb proteins is identified and designated E3RSIκBs, which represents a family of receptor proteins that are core components of a class of ubiquitin ligases.
The IκB Kinase (IKK) Complex Is Tripartite and Contains IKKγ but Not IKAP as a Regular Component*
TLDR
It is concluded that while IKKγ is a stoichiometric component of the IKK complex, obligatory for NF-κB signaling, IKAP is not associated with IKKs and plays no specific role in cytokine-induced NF-σκB activation.
A Novel Specific Role for IκB Kinase Complex-associated Protein in Cytosolic Stress Signaling*
TLDR
A novel role for the IκB kinase complex-associated protein (IKAP) in the regulation of activation of the mammalian stress response via the c-Jun N-terminal kinase (JNK)-signaling pathway is demonstrated and the results point to a role of JNK signaling in familial dysautonomia.
NIBP, a Novel NIK and IKKβ-binding Protein That Enhances NF-κB Activation*
TLDR
The data demonstrate that NIBP, by interacting with NIK and IKKβ, is a new enhancer of the cytokine-induced NF-κB signaling pathway, and it is demonstrated by immunohistochemistry that N IBP expression in the brain is localized to neurons.
The Beginning of the End: IκB Kinase (IKK) and NF-κB Activation*
  • M. Karin
  • Biology
    The Journal of Biological Chemistry
  • 1999
TLDR
Three-dimensional structures of NF-kBzIkB ternary complexes were solved, and fascinating structures indicate that the ankyrin repeats of IkBa form a slightly bent cylinder through a stacked arrangement of a-helices that compose their ankyrIn repeats.
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Activation of the transcription factor nuclear factor kappa B (NF-κB) is controlled by sequential phosphorylation, ubiquitination, and degradation of its inhibitory subunit IκB. A large multiprotein
THE NF-κB AND IκB PROTEINS: New Discoveries and Insights
▪ Abstract The transcription factor NF-κB has attracted widespread attention among researchers in many fields based on the following: its unusual and rapid regulation, the wide range of genes that it
IκB Kinase-β: NF-κB Activation and Complex Formation with IκB Kinase-α and NIK
TLDR
Overexpression of a catalytically inactive form of IKK-β blocked cytokine-induced NF-κB activation and suggested that an active IκB kinase complex may require three distinct protein kinases.
NF-κB-inducing kinase activates IKK-α by phosphorylation of Ser-176
TLDR
The phosphorylation of IKK-α on Ser-176 by NIK may be required for cytokine-mediated NF-κB activation, which is shown to be a dominant negative inhibitor of interleukin 1- and tumor necrosis factor-induced NF-KKB activation.
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TLDR
Results indicate that Nik and MEKK1 independently activate the IKK complex and that the kinase activities of IKKalpha and IKKbeta are differentially regulated by two upstream kinases, NIK andMEKK1, which are responsive to distinct stimuli.
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TLDR
A critical signal response domain in IkBa is defined that coordinately controls the biologic activities of IkBa and NF-k Bi n response to viral and immune stimuli.
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TLDR
IKK turns out to be the long-sought-after protein kinase that mediates the critical regulatory step in NF-κB activation, and phosphorylates IκBs on the sites that trigger their degradation.
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TLDR
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