Relevant bibliographies by topics / I-kappa B kinase epsilon

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  1. Journal articles
  2. Dissertations / Theses
  3. Conference papers
  4. Reports

Academic literature on the topic 'I-kappa B kinase epsilon'

Author: Grafiati
Published: 4 June 2021
Last updated: 11 February 2022

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Journal articles on the topic "I-kappa B kinase epsilon"

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Robe, PierreAlain, Nadège Dubois, Sharon Berendsen, Aurélie Henry, Minh Nguyen, and Vincent Bours. "I-Kappa-B Kinase-epsilon activates nuclear factor-kappa B and STAT5B and supports glioblastoma growth but amlexanox shows little therapeutic potential in these tumors." Cancer Translational Medicine 4, no. 1 (2018): 1. http://dx.doi.org/10.4103/ctm.ctm_3_18.

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Marsili, Giulia, Marco Sgarbanti, Anna Lisa Remoli, Edvige Perrotti, Chiara Acchioni та Angela Battistini. "PS1-095 Deregulation of I-kappa-B kinase epsilon (IKK-ε) in breast cancer: & #8232;effects on IRF1 activity". Cytokine 56, № 1 (2011): 41. http://dx.doi.org/10.1016/j.cyto.2011.07.127.

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Sgarbanti, Marco, Giulia Marsili, Anna Lisa Remoli, et al. "CS03-5. IRF-1 phosphorylation by I-kappa-B kinase epsilon impairs IFN beta stimulation in activated CD4+ T cells." Cytokine 56, no. 1 (2011): 9. http://dx.doi.org/10.1016/j.cyto.2011.07.318.

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Zhang, L., L. Wang, W. Chen, et al. "The expression of inhibitor of nuclear factor kappa-B kinase epsilon (IKKe) in human aortic aneurysm." Folia Morphologica 76, no. 3 (2017): 372–78. http://dx.doi.org/10.5603/fm.a2017.0016.

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Seccareccia, E., M. Pinard, N. Wang, et al. "The inhibitor of kappa B kinase-epsilon regulates MMP-3 expression levels and can promote lung metastasis." Oncogenesis 3, no. 8 (2014): e116-e116. http://dx.doi.org/10.1038/oncsis.2014.28.

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Zhou, Ruyuan, Qian Zhang, and Pinglong Xu. "TBK1, a central kinase in innate immune sensing of nucleic acids and beyond." Acta Biochimica et Biophysica Sinica 52, no. 7 (2020): 757–67. http://dx.doi.org/10.1093/abbs/gmaa051.

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Abstract Sensing of intracellular and extracellular environments is one of the fundamental processes of cell. Surveillance of aberrant nucleic acids, derived either from invading pathogens or damaged organelle, is conducted by pattern recognition receptors (PRRs) including RIG-I-like receptors, cyclic GMP-AMP synthase, absent in melanoma 2, and a few members of toll-like receptors. TANK-binding kinase 1 (TBK1), along with its close analogue I-kappa-B kinase epsilon, is a central kinase in innate adaptor complexes linking activation of PRRs to mobilization of transcriptional factors that transcribe proinflammatory cytokines, type I interferon (IFN-α/β), and myriads interferon stimulated genes. However, it still remains elusive for the precise mechanisms of activation and execution of TBK1 in signaling platforms formed by innate adaptors mitochondrial antiviral signaling protein (MAVS), stimulator of interferon genes protein (STING), and TIR-domain-containing adapter-inducing interferon-β (TRIF), as well as its complex regulations. An atlas of TBK1 substrates is in constant expanding, setting TBK1 as a key node of signaling network and a dominant player in contexts of cell biology, animal models, and human diseases. Here, we review recent advancements of activation, regulations, and functions of TBK1 under these physiological and pathological contexts.
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Siddiqui, M. Amir, Badruddeen, Juber Akhtar, Shahab Uddin M.S., Mohammad Irfan Khan, and Mohammad Khalid. "Molecular mechanism of interactions between chrysin and I-kappa-B kinase epsilon (IKKe)/tank binding kinase-1(TBK1): Cell-based assay and in silico molecular docking studies." Journal of Biomolecular Structure and Dynamics 38, no. 2 (2019): 589–96. http://dx.doi.org/10.1080/07391102.2019.1581086.

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Fischer, Fabian A., Linda F. M. Mies, Sohaib Nizami та ін. "TBK1 and IKKε act like an OFF switch to limit NLRP3 inflammasome pathway activation". Proceedings of the National Academy of Sciences 118, № 38 (2021): e2009309118. http://dx.doi.org/10.1073/pnas.2009309118.

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NACHT, LRR, and PYD domains–containing protein 3 (NLRP3) inflammasome activation is beneficial during infection and vaccination but, when uncontrolled, is detrimental and contributes to inflammation-driven pathologies. Hence, discovering endogenous mechanisms that regulate NLRP3 activation is important for disease interventions. Activation of NLRP3 is regulated at the transcriptional level and by posttranslational modifications. Here, we describe a posttranslational phospho-switch that licenses NLRP3 activation in macrophages. The ON switch is controlled by the protein phosphatase 2A (PP2A) downstream of a variety of NLRP3 activators in vitro and in lipopolysaccharide-induced peritonitis in vivo. The OFF switch is regulated by two closely related kinases, TANK-binding kinase 1 (TBK1) and I-kappa-B kinase epsilon (IKKε). Pharmacological inhibition of TBK1 and IKKε, as well as simultaneous deletion of TBK1 and IKKε, but not of either kinase alone, increases NLRP3 activation. In addition, TBK1/IKKε inhibitors counteract the effects of PP2A inhibition on inflammasome activity. We find that, mechanistically, TBK1 interacts with NLRP3 and controls the pathway activity at a site distinct from NLRP3-serine 3, previously reported to be under PP2A control. Mutagenesis of NLRP3 confirms serine 3 as an important phospho-switch site but, surprisingly, reveals that this is not the sole site regulated by either TBK1/IKKε or PP2A, because all retain the control over the NLRP3 pathway even when serine 3 is mutated. Altogether, a model emerges whereby TLR-activated TBK1 and IKKε act like a “parking brake” for NLRP3 activation at the time of priming, while PP2A helps remove this parking brake in the presence of NLRP3 activating signals, such as bacterial pore-forming toxins or endogenous danger signals.
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Azuma, Kotaro, Kazuhiro Ikeda, Takashi Suzuki, Kenjiro Aogi, Kuniko Horie-Inoue та Satoshi Inoue. "TRIM47 activates NF-κB signaling via PKC-ε/PKD3 stabilization and contributes to endocrine therapy resistance in breast cancer". Proceedings of the National Academy of Sciences 118, № 35 (2021): e2100784118. http://dx.doi.org/10.1073/pnas.2100784118.

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Increasing attention has been paid to roles of tripartite motif–containing (TRIM) family proteins in cancer biology, often functioning as E3 ubiquitin ligases. In the present study, we focus on a contribution of TRIM47 to breast cancer biology, particularly to endocrine therapy resistance, which is a major clinical problem in breast cancer treatment. We performed immunohistochemical analysis of TRIM47 protein expression in 116 clinical samples of breast cancer patients with postoperative endocrine therapy using tamoxifen. Our clinicopathological study showed that higher immunoreactivity scores of TRIM47 were significantly associated with higher relapse rate of breast cancer patients (P = 0.012). As functional analyses, we manipulated TRIM47 expression in estrogen receptor–positive breast cancer cells MCF-7 and its 4-hydroxytamoxifen (OHT)-resistant derivative OHTR, which was established in a long-term culture with OHT. TRIM47 promoted both MCF-7 and OHTR cell proliferation. MCF-7 cells acquired tamoxifen resistance by overexpressing exogenous TRIM47. We found that TRIM47 enhances nuclear factor kappa-B (NF-κB) signaling, which further up-regulates TRIM47. We showed that protein kinase C epsilon (PKC-ε) and protein kinase D3 (PKD3), known as NF-κB–activating protein kinases, are directly associated with TRIM47 and stabilized in the presence of TRIM47. As an underlying mechanism, we showed TRIM47-dependent lysine 27–linked polyubiquitination of PKC-ε. These results indicate that TRIM47 facilitates breast cancer proliferation and endocrine therapy resistance by forming a ternary complex with PKC-ε and PKD3. TRIM47 and its associated kinases can be a potential diagnostic and therapeutic target for breast cancer refractory to endocrine therapy.
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Diaz-Meco, M. T., M. M. Municio, P. Sanchez, J. Lozano, and J. Moscat. "Lambda-interacting protein, a novel protein that specifically interacts with the zinc finger domain of the atypical protein kinase C isotype lambda/iota and stimulates its kinase activity in vitro and in vivo." Molecular and Cellular Biology 16, no. 1 (1996): 105–14. http://dx.doi.org/10.1128/mcb.16.1.105.

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The members of the atypical subfamily of protein kinase C (PKC) show dramatic structural and functional differences from other PKC isotypes. Thus, in contrast to the classical or novel PKCs, they are not activated by diacylglycerol or phorbol esters. However, the atypical PKCs are the target of important lipid second messengers such as ceramide, phosphatidic acid, and 3'-phosphoinositides. The catalytic and pseudosubstrate sequences in the two atypical PKCs (lambda/iota PKC and zeta PKC) are identical but are significantly different from those of conventional or novel PKCs. It has been shown that microinjection of a peptide with the sequence of the pseudosubstrate of the atypical PKC isotypes but not of alpha PKC or epsilon PKC dramatically inhibited maturation and NF-kappa B activation in Xenopus oocytes, as well as reinitiation of DNA synthesis in quiescent mouse fibroblasts. This indicates that either or both atypical isoforms are important in cell signalling. Besides the pseudosubstrate, the major differences in the sequence between lambda/iota PKC and zeta PKC are located in the regulatory domain. Therefore, any functional divergence between the two types of atypical PKCs will presumably reside in that region. We report here the molecular characterization of lambda-interacting protein (LIP), a novel protein that specifically interacts with the zinc finger of lambda/iota PKC but not zeta PKC. We show in this paper that this interaction is detected not only in vitro but also in vivo, that LIP activates lambda/iota PKC but not zeta PKC in vitro and in vivo, and that this interaction is functionally relevant. Thus, expression of LIP leads to the transactivation of a kappa B-dependent promoter in a manner that is dependent on lambda/iota PKC. To our knowledge, this is the first report on the cloning and characterization of a protein activator of a PKC that binds to the zinc finger domain, which has so far been considered a site for binding of lipid modulators. The fact that LIP binds to lambda/iota PKC but not to the highly related zeta PKC isoform suggests that the specificity of the activation of the members of the different PKC subfamilies will most probably be accounted for by proteins like LIP rather than by lipid activators.
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Dissertations / Theses on the topic "I-kappa B kinase epsilon"

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Weissmann, Laís 1989. "A serina quinase IKK epsilon (IKKe) é importante para a ação e sinalização da insulina e leptina no hipotálamo de camundongos obesos." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311556.

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Orientador: Patrícia de Oliveira Prada<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas<br>Made available in DSpace on 2018-08-23T05:33:45Z (GMT). No. of bitstreams: 1 Weissmann_Lais_M.pdf: 2304567 bytes, checksum: b275887306c298a5ec1fd2910b146e00 (MD5) Previous issue date: 2013<br>Resumo: Recentemente, demonstrou-se que IkB quinase e (IKK?) aumenta a resistência à insulina (RI) induzida por dieta hiperlipídica em tecido adiposo e hepático. Assim, os objetivos do presente estudo foram investigar: 1) a expressão e ativação de IKK? no hipotálamo de camundongos DIO e db/db; 2) o papel da IKK? hipotalâmica no metabolismo energético e da glicose, e na ação e sinalização da insulina e leptina. Observamos maior expressão e ativação de IKK? no hipotálamo de camundongos db/db e DIO quando comparados aos controles. Cinco dias de injeção intracerebroventricular (ICV) de CAY (inibidor farmacológico da IKK?) ou de IKK? siRNA, via mini-bomba ICV, reduziu 80% da atividade de IKK?, a fosforilação do IRS1Ser307 e não alterou a fosforilação de IKK?/? em hipotálamo. A inibição IKK? (ICV): reduziu a adiposidade e ingestão alimentar, aumentou o consumo de O2 e expressão de UCP-1 no adiposo marrom, melhorou os efeitos anorexigênicos da insulina e de leptina, aumentou a fosforilação do receptor de insulina, da AKT, JAK2 e STAT3 em hipotálamo de camundongos DIO e db/db. Esses resultados persistiram com pair-feeding e pair-weight. A inibição com CAY (ICV) reduziu: a glicemia de jejum, produção hepática de glicose e expressão da PEPCK em fígado de animais DIO e db/db. Em resumo, os dados sugerem que IKK? hipotalâmica está ativada em modelos de obesidade e participa no desenvolvimento da resistência à insulina e leptina. Sua inibição reduz a adiposidade, ingestão alimentar e aumenta o gasto energético. A IKK? além de influenciar o metabolismo energético, também tem um papel no metabolismo da glicose de animais obesos. Assim, pode-se sugerir que a IKK? representa uma ligação entre a obesidade e resistência à insulina e leptina no hipotálamo e pode ser um alvo terapêutico para a resistência à insulina, obesidade e diabetes<br>Abstract: It was demonstrated that IkB kinase epsilon (IKK?) increased insulin resistance (IR) in liver and adipose tissue of diet-induced obesity (DIO) mice. The aims of this study are to investigate: 1) the expression and activation of IKK? in the hypothalamus from DIO mice and db/db, 2) the role of hypothalamic IKK? in the energy and glucose metabolism, and in insulin and leptin action/signaling. We observed increased expression and activation of IKK? in the hypothalamus from db/db and DIO mice compared with controls. Five days of intracerebroventricular (ICV) injections of CAY (pharmacological inhibitor of IKK?) or siRNA, via ICV mini-pump, reduced 80% of IKK? activity as well asthe phosphorylation of IRS1Ser307 and did not alter the phosphorylation of IKK?/? in hypothalamus from obese mice. Inhibition of IKK? (ICV) reduced fat mass, food intake and increased O2 consumption and expression of UCP-1 in the brown adipose tissue, improved anorexigenic effects of leptin and insulin, increased insulin receptor, AKT, JAK2 and STAT3 phosphorylation in the hypothalamus of DIO and db/db mice. These results persisted even if in pair-fed and pair-weight mice. Inhibition of IKK? with ICV CAY reduced: fasting glycemia, hepatic glucose production and the expression of PEPCK in liver of DIO and db/db animals. In summary, the data suggest that hypothalamic IKK? is activated in models of obesity and participates in the development of insulin and leptin resistance. Its inhibition reduces adiposity, food intake and increases energy expenditure. Hypothalamic IKK? influences the energy and glucose metabolism in obese mice. Thus, it can be suggested that the IKK? represents a link between obesity and insulin resistance in the hypothalamus and may be a new therapeutic target to treat insulin resistance, obesity and diabetes<br>Mestrado<br>Clinica Medica<br>Mestra em Clínica Médica
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Patel, Meghana. "Inhibitor of kappa B kinase epsilon (IKKε), the metabolic syndrome and atherosclerosis". Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648358.

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Gosemärker, Anna Teresa. "Charakterisierung der humanen und murinen I-kappa-B-Kinase-beta--Promotoren zur Analyse der gewebsspezifischen Variationen in der Zusammensetzng des I-kappa-B-Kinase-Komplexes." [S.l. : s.n.], 2008. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-64393.

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Prescott, Jack. "Interrogating novel functions of the I kappa B kinases via CRISPR-Cas9 gene editing and small molecule inhibition." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/277025.

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The NF-kB signalling pathway is a critical mediator of the cellular responses to inflammatory cytokines. The IκB kinase (IKK) complex, which is composed of two catalytic subunits (IKKα and IKKβ) and one regulatory subunit (IKKγ/NEMO) acts as the master regulator of NF-κB transcription factor activity. Seminal genetic studies in knockout (KO) mouse embryonic fibroblasts (MEFs) have defined two pathways of NF-κB activation; a canonical pathway, activated in response to cytokines such as TNFα/IL-1β, that requires NEMO and predominantly IKKβ catalytic activity; and a non-canonical pathway, activated in response to a subset of TNF-family cytokines, which requires IKKα and NIK kinase. We have generated and validated CRISPR-Cas9 IKKα, IKKβ and IKKα/β DKO HCT116 colorectal cancer cell lines to interrogate novel functions of the I kappa B kinases in colorectal cancer, including the relative contributions of these kinases to the activation of NF-κB signalling pathways downstream of TNFα induction. Contrary to the seminal studies in KO MEFs, IKKα appeared to make a more significant contribution to canonical NF-κB induction in these cells than IKKβ. Western blot studies demonstrated that both IKKs contributed to the phosphorylation and degradation of IκB and the phosphorylation of the NF-κB subunit, p65 at Serine 536. However, high-content immunofluorescence studies demonstrated that IKKα KO cells were defective in TNFα-induced nuclear translocation of p65 compared to WT and IKKβ KO cells. Additionally, NF-κB-driven luciferase reporter assays showed that IKKα, but not IKKβ, KO cells exhibited significantly reduced NF-κB-dependent gene expression following TNFα stimulation. We also have evidence to suggest that the phosphorylation site at Serine 468 on p65, previously defined as an IKKβ-dependent site, is in-fact an IKKα-dependent site in these cells. Furthermore, IKKα knockout revealed a potentially important role for IKKα activity in preventing the stabilisation of NIK protein following prolonged TNFα stimulation. RNA sequencing analysis of wild-type, IKKα KO, IKKβ KO and IKKα/β DKO cells stimulated with TNFα was performed to identify genes whose expression were differentially deregulated by IKK KO. These analyses confirmed the importance of IKKα for canonical NF-κB gene expression. Furthermore, IKKβ knockout had unexpected effects on the expression of a broad range of genes involved in chromatin organisation, cytoskeletal organisation, mitotic cell cycle control and the DNA damage response. During the characterisation of IKK KO cells it was discovered that the expression of NEMO was downregulated at the protein, but not mRNA level by approximately 50% in IKKα KO cells and 90% in IKKα/β DKO cells. IKKβ KO cells, meanwhile, exhibited wild-type NEMO expression. Emetine-chase and radioactive pulse chase labelling experiments demonstrated that the half-life of NEMO in IKKα and IKKα/β DKO cells was significantly shortened due to enhanced proteasomal turnover. Bioinformatics analyses predicted significant regions of intrinsic structural disorder within NEMO, particularly at the N- and C-termini, the former of which overlapped with the IKK binding domain. On this basis, the susceptibility of NEMO to in vitro degradation by the 20S proteasome was examined, with NEMO proving be a highly effective substrate of the 20S proteasome. Importantly, IKKα and IKKβ were both shown to protect NEMO from proteasomal degradation, leading us to propose a model whereby interaction with IKK kinase subunits sequesters/masks intrinsically disordered regions in NEMO that would otherwise make NEMO a highly effective substrate for ubiquitin-dependent and/or ubiquitin-independent proteasomal degradation. BMS-345541 is a commercially available allosteric inhibitor of IKKβ that has been used extensively in numerous studies, including a report that proposed novel functions for IKKβ in mitotic cell cycle progression (Blazkova et al., 2007). Similar antiproliferative effects to those reported by Blazkova et al., were observed during the characterisation of a novel ATP-competitive inhibitor of IKKβ, AZD2230. In depth characterisation of the selectivity of AZD2230 and BMS-345541, however, revealed that the antiproliferative effects of AZD2230 and BMS-345541 are, in fact, due to off-target inhibition, potentially at the level of RNA Polymerase II C-terminal domain phosphorylation, and hence general transcription. Collectively, these studies reveal novel functions of the IKK kinases in NF-κB signalling and inform therapeutic strategies for targeting chronic canonical NF-κB activation in colorectal cancer.
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Harris, Jennifer. "Regulation of nuclear factor kappa B subunit c-Rel through phosphorylation by two IKK-related kinases, IKK epsilon and TBK-1." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82250.

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The nuclear factor kappaB (NF-kappaB) transcription factors are key regulators of immunomodulatory genes regulation. NF-kappaB activity is regulated through the phosphorylation of inhibitory proteins (IkappaBs) by the IkappaB kinase (IKK) complex (IKK alpha/beta/gamma), leading to IkappaB degradation and NF-kappaB translocation to the nucleus where they promote transcription of immunoregulatory genes. Moreover, cRel and p65 activities are also regulated by direct phosphorylation of their transactivation domain. Recently, two IKK non-canonical homologues, IKKepsilon and TBK-1 (TANK binding kinase-1) have been identified with functions distinct from the classical IKKalpha/IKKbeta. TBK-1/IKKepsilon trigger antiviral immunity through direct phosphorylation of the IRF3/IRF7 transcription factors, which are key regulators of the interferon response. Since IKKepsilon modulates the activity of IRF3/IRF7, it is of interest to assess whether IKKepsilon/TBK-1 also regulates the transactivation activity of NF-kappaB. Our hypothesis was that IKKepsilon/TBK-1 modulates the activity of cRel by direct phosphorylation of its transactivation domain (TD). In this study, we demonstrate that IKKepsilon and TBK-1 directly phosphorylate cRel in vitro and in vivo. Two of the three consensus sequences recognized by IKKepsilon/TBK-1 in the cRel TD are directly phosphorylated by IKKepsilon. cRel was translocated to the nucleus in cells expressing wild type versus kinase dead variant. The expression of IKKepsilon increases c-Rel transactivation in reporter gene assays. Serine to alanine mutation was further used to characterize the function of this phosphorylation at the level of nuclear translocation and transactivation potential using immunofluorescence and reporter gene assay. Furthermore, co-expression studies revealed that IKKepsilon and not the kinase dead variant is responsible for cRel degradation in a dose-dependent manner and this effect is partially revert
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Rice, Julie Ann. "Molecular mediators of alpha v beta 3-induced NF-[kappa] B activation in endothelial cell survival /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/6360.

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Chéreau, Fanny. "ABIN-2, un nouvel activateur de NF-kappaB en réponse aux agents génotoxiques : implication de la poly-ubiquitination." Paris 7, 2012. http://www.theses.fr/2012PA077004.

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Les facteurs de transcription NF-kappaB sont régulés au travers de différentes voies de signalisation, qui convergent cependant toutes vers un complexe IKK composé de deux sous-unités kinases IKKalpha et IKKbeta ainsi que d'une sous-unité régulatrice NEMO. Bien que les fonctions de chacune des sous-unités aient été étudiées, le rôle spécifique de la kinase IKKalpha ainsi que les mécanismes impliqués dans sa régulation restent encore mal élucidés. En particulier, ses partenaires d'interaction sont peu connus. ABIN-2 a été identifié par l'équipe comme partenaire d'IKKalpha par une approche de protéomique et mon travail de thèse a consisté à caractériser le rôle d'ABIN-2 dans la régulation de NF-kappaB médiée par IKKalpha. J'ai montré qu'ABIN-2 est nécessaire à l'activation de NF-kappaB induite en réponse à des agents génotoxiques ainsi qu'en réponse à des inductions longues au TNFalpha, via l'activation de la kinase IKKalpha. J'ai aussi étudié deux domaines structuraux d'ABIN-2 appelés UBAN et ZF et montré par l'étude de mutations ponctuelles de ces domaines qu'ils sont essentiels pour l'activation de NF-kappaB médiée par IKKalpha. Par ailleurs, j'ai montré que ces domaines sont essentiels à la reconnaissance de chaînes poly-ubiquitinées en K63 et linéaires par ABIN-2 ainsi que pour la poly-ubiquitination non dégradative en K63 d'ABIN-2. A la lumière de nos résultats, nous proposons un modèle selon lequel à la fois la poly-ubiquitination d'ABIN-2 et sa capacité de reconnaissance de partenaires poly-ubiquitinés seraient nécessaires pour l'activation d'IKKalpha et de NF-kappaB<br>NF-kappaB transcription factors are regulated through different pathways but they all converge at the level of thé IKK complex, which is composed of two catalytic subunits IKKalpha and IKKbeta and a regulatory subunit NEMO. Even though the function of each subunit has been studied, the specific role of IKKalpha and its regulation remain poorly elucidated. In particular, the IKKalpha -interacting proteins involved in the regulation of its activity are poorly characterized. In our group, ABIN-2 has been identified as an interacting partner of IKKalpha by a proteomic approach and my Ph. D. Research project aimed to characterize the specific role of ABIN-2 in the regulation of IKKalpha -mediated NF-kappaB activation. I demonstrated that ABIN-2 is required for NF-kappaB activation as a late response to TNFalpha and genotoxic stress stimulation, through the activation of IKKalpha. In addition, we studied two structural domains of ABIN-2, named UBAN and ZF and showed by mutational analysis that these domains are essential for optimal NF-kappaB activation mediated by IKKalpha. Moreover, I showed that these domains are necessary for ABIN-2 to recognize K63-linked and linear poly-ubiquitin chains as well as for nondegradative K63-linked poly-ubiquitination of ABIN-2 itself. These results suggest that ABIN-2 poly-ubiquitination altogether with ABIN-2 binding to poly-ubiquitinated partners are necessary to activate IKKalpha and subsequently NF-kappaB
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Sebban, Hélène. "Analyse moléculaire de mutations de NEMO causant des maladies génétiques humaines." Paris 7, 2007. http://www.theses.fr/2007PA077105.

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Le facteur de transcription NF-kB est activé par de nombreux stimuli, parmi lesquels des cytokines comme le TNF ou l'ILl, des produits bactériens comme le LPS, des protéines virales comme Tax ou différentes formes de stress. La phosphorylation d'IB par le complexe IKK induit son ubiquitination et sa dégradation par le protéasome. NF-kB peut alors être transloqué vers le noyau et réguler l'expression de gènes participant aux processus d'inflammation, de réponse immunitaire, d'adhésion cellulaire, de protection contre l'apoptose ou de contrôle du cycle cellulaire. IKK est constitué de deux sous-unités catalytiques IKK1 et IKK2, et d'une sous-unité régulatrice NEMO (NF-kB Essential MOduIator). Encore récemment, aucune maladie génétique n'était liée à un dysfonctionnement de la voie NF-kB. Deux maladies génétiques humaines liées à une mutation sur l'X du gène codant pour NEMO ont été identifiées : Incontinentia Pigmenti et la Dysplasie Ectodermique Anhidrotique avec Immunodéficience. Elles révèlent l'importance de la voie NF-kB dans l'homéostasie de l'épiderme, le développement cutané, l'immunité acquise et innée, confirmant le rôle clé de la protéine NEMO dans la régulation de la voie NF-kB. La relation structure-fonction de NEMO, et ses interactions avec les protéines impliquées dans les différentes voies conduisant à l'activation de NF-kB, restent mal connues. Utilisant comme outils des mutations de NEMO identifiées chez des patients IP et EDA-ID, essentiellement des mutations faux-sens et des délétions d'un ou plusieurs acides aminés, situées dans différents domaines de la molécule, nous essayons de comprendre le mode de fonctionnement de NEMO au sein d'IKK<br>NF-kB is activated by several stimuli, among them cytokines like TNF or IL1, bacterian products like LPS, viral proteins like Tax and different kind of stress. Phosphorylation of IkBa by IKK complex induces its ubiquitination and degradation by the proteasome. NF-kB can be translocated into the nucleus and regulate genes expression involved in the inflammation process, immune response, cellular adhesion, protection against apoptosis and proliferation. IKK complex is constituted by two catalytic subunits IKK1 and IKK2, and a regulator subunit NEMO (NF-kB Essential MOduIator). Until recently, not any genetic disease was linked to the NF-kB pathway. Two genetic pathologies associated with an X-linked mutation into the gene encoding for NEMO have been identified. These two human pathologies (Incontinentia Pigmenti (IP) and Anhidrotic Ectodermal Dysplasia with Immunodeficiency (EDA-ID)) show the importance of the NF-kB pathway in epidermic homeostasia, cutaneous development, natural and acquired immunity, confirming the critical role of NEMO in the NF-kB pathway regulation. The relation structure-fonction of NEMO, and its interactions with proteins implicated in the different pathways driving to NF-kB activation, are still not well known. By using NEMO mutations identified in IP and EDA-ID patients, essentially missense mutations and short deletions, localized in different domains of NEMO, we are trying to understand how NEMO fonctions within IKK complex
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Menagh, Gillian. "The regulation of Toll-like receptor (TLR)-stimulated inducible inhibitory kappa B kinase (IKK-i) expression in murine macrophages." Thesis, University of Strathclyde, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432751.

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Guo, Beichu. "Interaction of PKCbeta with CARMA1 mediates B cell receptor-induced NF-kappaB activation /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/8348.

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Conference papers on the topic "I-kappa B kinase epsilon"

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Guo, Jianping, Anna Cheng, Evita B. Henderson-Jackson, Donghwa Kim, Mokenge Malafa та Domenico Coppola. "Abstract LB-144: I-kappa-B kinase (IKK)ε expression in pancreatic ductal adenocarcinoma". У Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-lb-144.

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Reports on the topic "I-kappa B kinase epsilon"

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Cheng, Kun, and Bin Qin. Targeting the I-Kappa-B Kinase Epsilon (IKKe) for Breast Cancer Therapy. Defense Technical Information Center, 2009. http://dx.doi.org/10.21236/ada554623.

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