Regulation and Function of IKK and IKK-Related Kinases

@article{Hcker2006RegulationAF,
  title={Regulation and Function of IKK and IKK-Related Kinases},
  author={Hans H{\"a}cker and Michael Karin},
  journal={Science's STKE},
  year={2006},
  volume={2006},
  pages={re13 - re13}
}
Members of the nuclear factor kappa B (NF-κB) family of dimeric transcription factors (TFs) regulate expression of a large number of genes involved in immune responses, inflammation, cell survival, and cancer. NF-κB TFs are rapidly activated in response to various stimuli, including cytokines, infectious agents, and radiation-induced DNA double-strand breaks. In nonstimulated cells, some NF-κB TFs are bound to inhibitory IκB proteins and are thereby sequestered in the cytoplasm. Activation… Expand
The IκB kinase complex: master regulator of NF-κB signaling
TLDR
How these studies have identified a unique inhibitor of pro-inflammatory NF-κB signaling, an unforeseen role for IKKα in the classical NF-kkB pathway, and a novel functional domain in IKKβ that is not present in Ikkα is described. Expand
The NF-kappaB family of transcription factors and its regulation.
TLDR
The NF-kappaB pathway is a paradigm for understanding general principles of signal transduction and gene regulation as well as other pathway-specific mediators, and the transcription factors are themselves extensively modified. Expand
Elucidating dynamic protein-protein interactions and ubiquitination in NF-κB signaling pathways.
TLDR
The protocols routinely used in the laboratories to examine ubiquitin-editing and NF-κB signaling are summarized. Expand
The NFk B Family of Transcription Factors and Its Regulation
Nuclear factor-kB (NF-kB) consists of a familyof transcription factors that play critical roles in inflammation, immunity, cell proliferation, differentiation, and survival. Inducible NF-kBExpand
A20-binding Inhibitor of Nuclear Factor-κB (NF-κB)-2 (ABIN-2) Is an Activator of Inhibitor of NF-κB (IκB) Kinase α (IKKα)-mediated NF-κB Transcriptional Activity*
TLDR
It is demonstrated that IKKα and IKKβ both interact with ABIN-2 and impair its constitutive degradation by the proteasome, implying that ABin-2 acts as a positive regulator of NF-κB-dependent transcription by activating IKK α. Expand
The nuclear signaling of NF-κB: current knowledge, new insights, and future perspectives
TLDR
New insights into the nuclear events that govern NF-κB function will deepen the understanding of the elegant control of its transcriptional activity and better inform the potential rational design of therapeutics for NF-σκB-associated diseases. Expand
Priming IKKβ kinase for action.
TLDR
Two apparently conflicting earlier models of IKK β activation are resolved into a single unified model, and it is suggested that the IKKβ activation loop may integrate distinct 'upsteam' signals to activate NF-κB. Expand
IkB kinase b (IKKb/IKK2/IKBKB)—A key molecule in signaling to the transcription factor NF-kB
IKKb/IKBKB (IkB kinase beta), also designated as IKK2, was named after its function of phosphorylating IkB molecules, the inhibitors of NF-kB transcription factors. The kinase activity of IKKbExpand
Just the right amount of JNK: How nuclear factor-kappaB and downstream mediators prevent burn-induced intestinal injury.
TLDR
These studies demonstrate that both NFkB and JNK signaling are critical in determining the gut's response to thermal-induced intestinal injury and elevating caspase 3 is reflective of increased epithelial apoptosis and injury which, in turn, leads to worsening barrier function. Expand
Novel cross-talk within the IKK family controls innate immunity.
TLDR
The studies reveal that the canonical IKKs and the IKK-related kinases regulate each other by an intricate network involving phosphorylation of their catalytic and regulatory (NEMO and TANK) subunits to balance their activities during innate immunity. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 288 REFERENCES
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. Expand
IKK-γ is an essential regulatory subunit of the IκB kinase complex
TLDR
By using a monoclonal antibody against IKK-α, the IKK complex is purify to homogeneity from human cell lines and it is found that IKK is composed of similar amounts of IKK, α and β and two other polypeptides, for which the authors obtained partial sequences. Expand
Activation of Transcription Factor NF-κB Requires ELKS, an IκB Kinase Regulatory Subunit
TLDR
ELKS likely functions by recruiting IκBα to the IKK complex and thus serves a regulatory function for IKK activation, and is likely not protected from apoptosis in response to cytokines. Expand
Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.
TLDR
Recent progress has been made in understanding the details of the signaling pathways that regulate NF-kappaB activity, particularly those responding to the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1. Expand
IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex.
TLDR
By using a monoclonal antibody against IKK-alpha, this large, cytokine-responsive IkappaB kinase (IKK) complex is purified to homogeneity from human cell lines and it is found that IKK is composed of similar amounts of IKK, alpha and beta, and two other polypeptides are differentially processed forms of a third subunit, Ikk-gamma. Expand
IKK-1 and IKK-2: Cytokine-Activated IκB Kinases Essential for NF-κB Activation
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 multiproteinExpand
Positive and Negative Regulation of IκB Kinase Activity Through IKKβ Subunit Phosphorylation
TLDR
IKKβ, not IKKα, is the target for proinflammatory stimuli, and once activated, IKKβ autophosphorylated at a carboxyl-terminal serine cluster, decreased IKK activity and may prevent prolonged activation of the inflammatory response. Expand
Akt regulates basal and induced processing of NF-kappaB2 (p100) to p52.
TLDR
Observations show that Akt plays a role in activation of basal and induced non-canonical NF-kappaB activity, whereas kinase dead Akt or inhibition of phosphatidylinositol 3-kinase have the opposite effect. Expand
Akt Regulates Basal and Induced Processing of NF-κB2 (p100) to p52*
TLDR
Akt binds to and increases the activity of IKKα and thereby increases p52 production in cells, and observations show that Akt plays a role in activation of basal and induced non-canonical NF-κB activity. Expand
Activation by IKKα of a Second, Evolutionary Conserved, NF-κB Signaling Pathway
TLDR
It is shown that IKKα is required for B cell maturation, formation of secondary lymphoid organs, increased expression of certain NF-κB target genes, and processing of the NF-σκB2 (p100) precursor. Expand
...
1
2
3
4
5
...