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Mitogen-activated protein kinase kinase kinase 14

NF-kappaB-inducing kinase
This gene encodes mitogen-activated protein kinase kinase kinase 14, which is a serine/threonine protein-kinase. This kinase binds to TRAF2 and stimulates NF-kappaB activity. It shares sequence similarity with several other MAPKK kinases. It participates in an NF-kappaB-inducing signalling cascade common to receptors of the tumour-necrosis/nerve-growth factor (TNF/NGF) family and to the interleukin-1 type-I receptor. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: NF-kappaB, IkappaBalpha, IKKbeta, p65, I-kappa B Kinase
Papers on NF-kappaB-inducing kinase
Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: a comprehensive review.
Hassa et al., Zürich, Switzerland. In Mol Cancer, 2014
Several novel potential drug targets have been recently identified such as the BET bromodomain protein (BRD)-4, phosphoribosyl-pyrophosphate synthetase (PRPS)-2, macrodomain-containing mono-ADP-ribosyltransferase (ARTD)-9 (also known as PARP9), deltex-3-like E3 ubiquitin ligase (DTX3L) (also known as BBAP), NF-kappaB inducing kinase (NIK) and transforming growth factor beta receptor (TGFβR).This review highlights the new insights into the molecular basis of relapsed/refractory DLBCL and summarizes the most promising drug targets and experimental treatments for relapsed/refractory DLBCL, including the use of novel agents such as lenalidomide, ibrutinib, bortezomib, pidilizumab, epratuzumab, brentuximab-vedotin or CAR T cells, dual inhibitors, as well as mechanism-based combinatorial experimental therapies.
Structure of the nuclear factor κB-inducing kinase (NIK) kinase domain reveals a constitutively active conformation.
Wang et al., San Francisco, United States. In J Biol Chem, 2012
a molecular basis for the recent observation of gain-of-function activity for an N-terminal deletion mutant (DeltaN324) of NIK, leading to constitutive non-canonical NF-kappaB signaling with enhanced B-cell adhesion and apoptosis resistance.
MicroRNA-520e suppresses growth of hepatoma cells by targeting the NF-κB-inducing kinase (NIK).
Zhang et al., Tianjin, China. In Oncogene, 2012
NIK is one of the direct target genes of miR-520e.
Genetic lesions of the TRAF3 and MAP3K14 genes in classical Hodgkin lymphoma.
Küppers et al., Essen, Germany. In Br J Haematol, 2012
Genetic lesions of the TRAF3 and MAP3K14 genes in classical Hodgkin lymphoma.
NF-κB inducing kinase (NIK) modulates melanoma tumorigenesis by regulating expression of pro-survival factors through the β-catenin pathway.
Richmond et al., Nashville, United States. In Oncogene, 2012
NIK mediates both beta-catenin and NF-kappaB regulated transcription to modulate melanoma survival and growth
NIK prevents the development of hypereosinophilic syndrome-like disease in mice independent of IKKα activation.
Redecke et al., Memphis, United States. In J Immunol, 2012
NIK activity in nonhematopoietic cells controls Th2 cell development and prevents eosinophil-driven inflammatory disease, most likely using a signaling pathway that operates independent of the known NIK substrate IKKalpha.
NF-kappaB-inducing kinase (NIK) mediates skeletal muscle insulin resistance: blockade by adiponectin.
Bajaj et al., Galveston, United States. In Endocrinology, 2011
Adiponectin treatment inhibited NIK-induced NF-kappaB activation and restored insulin sensitivity by restoring phosphatidylinositol 3 kinase activation and subsequent serine-threonine kinase phosphorylation.
An atypical E3 ligase zinc finger protein 91 stabilizes and activates NF-kappaB-inducing kinase via Lys63-linked ubiquitination.
Lee et al., South Korea. In J Biol Chem, 2010
An atypical E3 ligase zinc finger protein 91 stabilizes and activates NF-kappaB-inducing kinase via Lys63-linked ubiquitination.
Peroxisome proliferator-activated receptor delta agonists attenuated the C-reactive protein-induced pro-inflammation in cardiomyocytes and H9c2 cardiomyoblasts.
Leu et al., Taipei, Taiwan. In Eur J Pharmacol, 2010
NF-kappaB inducing kinase (NIK) and NF-kappaB pathway also activated by CRP stimulation.
NF-kappaB inducing kinase (NIK) inhibitors: identification of new scaffolds using virtual screening.
Frederick et al., Namur, Belgium. In Bioorg Med Chem Lett, 2010
Among these, the inhibition of the NF-kappaB inducing kinase (NIK), a key enzyme of the NF-kappaB alternative pathway activation, represents a potential interesting approach.
Soluble and transmembrane TNF-like weak inducer of apoptosis differentially activate the classical and noncanonical NF-kappa B pathway.
Wajant et al., Würzburg, Germany. In J Immunol, 2010
In this study, we show that membrane TWEAK is superior to soluble variant of TWEAK (sTWEAK) with respect to the activation of the classical NF-kappaB pathway, whereas both TWEAK variants are potent inducers of TNFR-associated factor-2 depletion, NF-kappaB-inducing kinase accumulation and p100 processing, hallmarks of activation of the noncanonical NF-kappaB pathway.
TNF superfamily: a growing saga of kidney injury modulators.
Ortiz et al., Madrid, Spain. In Mediators Inflamm, 2009
TWEAK promotes the secretion of MCP-1 and RANTES through NF-kappaB RelA-containing complexes and upregulates CCl21 and CCL19 expression through NF-kappaB inducing kinase (NIK-) dependent RelB/NF-kappaB2 complexes.
The intertwining of structure and function: proposed helix-swapping of the SH2 domain of Grb7, a regulatory protein implicated in cancer progression and inflammation.
Lyons et al., Las Cruces, United States. In Crit Rev Immunol, 2009
Best known for its regulatory role in cell migration and tumor metastasis, Grb7 also regulates inflammation by coupling NF-kappaB-inducing kinase with erbB/EGFR family receptors.
Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling.
Karin et al., San Diego, United States. In Nat Immunol, 2008
The adaptor and signaling proteins TRAF2, TRAF3, cIAP1 and cIAP2 may inhibit alternative nuclear factor-kappaB (NF-kappaB) signaling in resting cells by targeting NF-kappaB-inducing kinase (NIK) for ubiquitin-dependent degradation, thus preventing processing of the NF-kappaB2 precursor protein p100 to release p52.
The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance.
Inoue et al., Tokyo, Japan. In Immunity, 2008
Ligation of RANK or CD40 on fetal thymic stroma in vitro induced mTEC development in a tumor necrosis factor-associated factor 6 (TRAF6)-, NF-kappaB inducing kinase (NIK)-, and IkappaB kinase beta (IKKbeta)-dependent manner.
(Un)expected roles of c-IAPs in apoptotic and NFkappaB signaling pathways.
Vucic et al., San Francisco, United States. In Cell Cycle, 2008
On the other hand, they regulate pro-survival NFkappaB signaling pathways: in the non-canonical pathway, by ubiquitination of NFkappaB-inducing kinase (NIK), and in the canonical pathway, by a yet-to-be-defined mechanism.
Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin.
Minato et al., Kyoto, Japan. In Nat Immunol, 2007
We provide evidence that such Cld3,4(hi) UEA-1(+) TECs represented the initial progenitors specified for Aire(+) mTECs, whose development crucially required NF-kappaB-inducing kinase and the adaptor molecule TRAF6.
Regulation of naive T cell function by the NF-kappaB2 pathway.
Sprent et al., Los Angeles, United States. In Nat Immunol, 2006
Here we show that mice deficient in NF-kappaB-inducing kinase have a complex phenotype consisting of immunosuppression mediated by CD25(-)Foxp3(-) memory CD4(+) cells and, in the absence of those cells, hyper-responsive naive CD4(+) T cells, which caused autoimmune lesions after adoptive transfer into hosts deficient in recombination-activating genes.
The NF-kappaB regulatory network.
Brasier, Galveston, United States. In Cardiovasc Toxicol, 2005
By contrast, the noncanonical NF-kappaB activation pathway involves activating the NF-kappaB inducing kinase (NIK) to stimulate IKKalpha-induced phosphorylation and proteolytic processing of the 100-kDa cytoplasmic NF-kappaB2 precursor.
Receptor-specific signaling for both the alternative and the canonical NF-kappaB activation pathways by NF-kappaB-inducing kinase.
Wallach et al., Israel. In Immunity, 2004
The NF-kappaB-inducing kinase (NIK) induces proteolytic processing of NF-kappaB2/p100 and, hence, the generation of NF-kappaB dimers such as p52:RelB but was suggested not to signal for the processing of IkappaB.
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