NIK/NF-kappaB2 regulated gene products.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE7219 | GEO | 2008/03/05
SECONDARY ACCESSION(S): PRJNA98289
REPOSITORIES: GEO
Similar Datasets
Project description:This study aims at identifying genes that are NIK/NF-kappaB2 responsive in murine dendritic cells matured in vivo. Experiment Overall Design: This study isolated dendritic cells from the spleens of Alymphoplasia or heterozygeous littlermates (wild type). Mice were eiter not treated as a reference or treated I.P. with 25 micrograms of LPS and 100 micrograms of agonistic anti-CD40 antibody. DCs were isolated 6 hours after treatment allowing in vivo maturation via both TLR and CD40 signals. DCs from 3 mice per group were pooled. Experiment was performed in triplicate.
2008-04-06 | E-GEOD-7219 | biostudies-arrayexpress
Project description:Systemic lupus erythematosus (SLE) is often considered a disease driven by autoreactive B cells and anti-nuclear antibodies. However, therapeutic targeting of B cells, for example through BAFF blockade, has been only partially effective in SLE. NF-κB Inducing Kinase (NIK) mediates non-canonical NF-κB signaling downstream of disease relevant TNF family members, such as BAFF, TWEAK, CD40, and OX40. We hypothesized that NIK inhibition might be more efficacious than BAFF blockade in lupus, and therefore generated highly selective and potent small molecule inhibitors (SMI) of NIK to test this hypothesis. RNASeq was used to investigate the effects of one of these SMIs of NIK, NIK SMI1, on TWEAK-stimulated Mouse renal proximal tubule-interstitial epithelial cells (RPTEC).
2017-10-26 | GSE89195 | GEO
Project description:Proper regulation of nuclear factor κB (NF-κB) transcriptional activity is required for normal lymphocyte function, and deregulated NF-κB signaling can facilitate lymphomagenesis. We demonstrate that the API2-MALT1 fusion oncoprotein created by the recurrent t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma induces proteolytic cleavage of NF-κB–inducing kinase (NIK) at arginine 325. NIK cleavage requires the concerted actions of both fusion partners and generates a C-terminal NIK fragment that retains kinase activity and is resistant to proteasomal degradation. The resulting deregulated NIK activity is associated with constitutive noncanonical NF-κB signaling, enhanced B cell adhesion, and apoptosis resistance. Our study reveals the gain-of-function proteolytic activity of a fusion oncoprotein and highlights the importance of the noncanonical NF-κB pathway in B lymphoproliferative disease. This study compares nine t(11;18)-positive MALT lymphomas (8 from the stomach and 1 from lung) and eight translocation negative MALT lymphomas (all from the stomach) using gene set enrichment analysis (GSEA). All cases were subjected to Affymetrix U133A and U133B microarray analysis. The cases used in this study are the same cases used for the study by Hamoudi et al. (2010) entitled "Differential expression of NF-kB target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism" with GEO reference number: GSE18736 and PubMed ID: http://www.ncbi.nlm.nih.gov/pubmed/20520640 All cases were subjected to non-specific filtering to eliminate non-variant probes, then the U133A and U133B probes were collapsed and the collapsed set was subjected to GSEA using the NF-kB target gene set as described in Hamoudi et al. (2010) study mentioned above. The 34 samples in this study are identical to the ones done in the previous series except that the gene set enrichment was done on just those 34 samples and not the complete set.
2011-01-30 | E-GEOD-25527 | biostudies-arrayexpress
Project description:Proper regulation of nuclear factor κB (NF-κB) transcriptional activity is required for normal lymphocyte function, and deregulated NF-κB signaling can facilitate lymphomagenesis. We demonstrate that the API2-MALT1 fusion oncoprotein created by the recurrent t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma induces proteolytic cleavage of NF-κB–inducing kinase (NIK) at arginine 325. NIK cleavage requires the concerted actions of both fusion partners and generates a C-terminal NIK fragment that retains kinase activity and is resistant to proteasomal degradation. The resulting deregulated NIK activity is associated with constitutive noncanonical NF-κB signaling, enhanced B cell adhesion, and apoptosis resistance. Our study reveals the gain-of-function proteolytic activity of a fusion oncoprotein and highlights the importance of the noncanonical NF-κB pathway in B lymphoproliferative disease.
2011-01-30 | GSE25527 | GEO
Project description:NF-κB-Inducing Kinase (NIK), which is essential for the activation of the noncanonical NF-κB pathway, regulates diverse processes in immunity, development, and disease. While recent studies have elucidated important functions of NIK in adaptive immune cells and cancer cell metabolism, the role of NIK in metabolic-driven inflammatory responses in innate immune cells remains unclear. Here we demonstrate that NIK-deficient bone marrow-derived macrophages exhibit defects in mitochondrial-dependent metabolism and oxidative phosphorylation (OXPHOS) functions that impair acquisition of a pro-repair, anti-inflammatory phenotype. Subsequently, NIK-deficient mice exhibit skewing of myeloid cells characterized by aberrant eosinophil, monocyte, and macrophage cell populations in the blood, bone marrow, and adipose tissue. Furthermore, NIK-deficient blood monocytes display hyperresponsiveness to bacterial lipopolysaccharide and elevated TNFα production ex vivo, indicative of systemic inflammation. These findings suggest that NIK is required for the metabolic rewiring of mitochondrial respiration that is critical for balancing pro- and anti-inflammatory myeloid immune cell functions. Overall, our work highlights a previously unrecognized role for NIK as a molecular rheostat that fine-tunes immunometabolism in innate immunity and suggests that metabolic dysfunction may be an important driver of inflammatory diseases caused by aberrant NIK expression or activity.
2023-01-20 | GSE223040 | GEO
Project description:Studies from global loss-of-function mutants suggest that alternative NF-kB downstream of NF-kB inducing kinase (NIK) is a cell-intrinsic negative regulator of osteogenesis. However, the interpretation of the osteoblast and/or osteocyte contribution to the bone phenotype is complicated by simultaneous osteoclast defects in these models. Therefore, we turned to a transgenic mouse model to investigate the direct role of NIK in the osteolineage. Osx-Cre;NT3 animals (NT3-Cre+), which bear a constitutively active NIK allele (NT3) driven by Osx-Cre, were compared to their Cre-negative, Control (Ctrl) littermates. NT3-Cre+ mice had elevated serum P1NP and CTX levels. Despite this high turnover state, microCT showed that constitutive activation of NIK resulted in a net increase in basal bone mass in both cortical and cancellous compartments. Furthermore, NT3-Cre+ mice exhibited a greater anabolic response following mechanical loading compared to controls. We next performed RNA-Seq on non-loaded and loaded tibiae to elucidate possible mechanisms underlying the increased bone anabolism seen in NT3-Cre+ mice. Hierarchical clustering revealed two main transcriptional programs: one loading-responsive and the other NT3 transgene-driven. Gene ontology (GO) analysis indicated a distinct upregulation of receptor, kinase and growth factor activities including Wnts, as well as a calcium-response signature in NT3-Cre+ limbs. The promoters of these GO-term associated genes, including many known to be bone-anabolic, were highly enriched for multiple kB recognition elements (kB-RE) relative to the background frequency in the genome. The loading response in NT3-Cre+ mice substantially overlapped (>90%) with Ctrl. Surprisingly, control animals had 10-fold more differentially expressed genes (DEGs) in response to loading. However, most top DEGs shared between genotypes had a high incidence of multiple kB-RE in their promoters. Therefore, both transcriptional programs (loading-responsive and NT3 transgene-driven) are modulated by NF-kB. Our studies uncover a previously unrecognized role for NF-kB in the promotion of both basal and mechanically-stimulated bone formation.
2019-06-25 | GSE133212 | GEO
Project description:The non-canonical NF-κB signaling cascade is essential for lymphoid organogenesis, B-cell maturation, osteoclast differentiation, and inflammation in mammals, whereas dysfunction of this system is associated with human diseases, including immunological disorders and cancer. While controlled expression of NF-κB Inducing Kinase (NIK) is the rate-limiting step in non-canonical NF-κB activation, mechanisms of inhibition remain largely unknown. Here, we report the identification of the sine oculis homeobox homolog family transcription factors SIX1 and SIX2 as essential inhibitory components of the non-canonical NF-κB signaling pathway. The developmentally silenced SIX-proteins are reactivated in differentiated macrophages by NIK-mediated suppression of the ubiquitin proteasome pathway. Consequently, SIX1 and SIX2 target a subset of inflammatory gene promoters and directly inhibit RelA and RelB trans-activation function in a negative feedback circuit. In support of a physiologically pivotal role for SIX-proteins in host immunity, human SIX1 transgene suppressed inflammation and promoted the recovery of mice from endotoxic shock. In addition, SIX1 and SIX2 protected RAS/p53-driven lung adenocarcinoma cells from inflammatory cell death induced by SMAC-mimetic chemotherapeutic agents, small-molecule activators of the non-canonical NF-κB pathway. Collectively, our study reveals a NIK-SIX signaling axis that fine-tunes inflammatory gene expression programs under both physiological and pathological conditions.
2019-03-22 | GSE126535 | GEO
Project description:2 This project is to identify the potential neddylation sites in human NF-kB inducing kinase (A.k.a. Map3K14). NIK-HA or NIK-HA in combination with FLAG-NEDD8 were co-expressed in HEK293T cells. NIK-HA were pulled down via denaturing immunoprecipitation protocol, subject to SDS-PAGE, in-gel trypsin digestion, and Nano LC-MS/MS Analysis. The potential peptides containing K-GG sites were identified.
2023-03-10 | PXD038653 | Pride
Project description:Purpose: The goal of this study is to determine the molecular mechanisms involved in the NIK regulation of α cell function. Methods: mRNA profiles of β-Gal control, NIK, and NIK(KA) overexpressed αTC1-6 cells were generated by deep sequencing using an Illumina Hiseq platform. Paired-end clean reads were aligned to the mouse reference genome(Ensemble_GRCm38.89) with TopHat (version 2.0.12), and the aligned reads were used to quantify mRNA expression by using HTSeq-count (version 0.6.1). Conclusion: Our study represents the first detailed analysis of NIK-overexpressing aTC1-6 cell transcriptomes, generated by RNA-seq technology. Our results show that 328 genes were upregulated and 48 genes were downregulated following NIK overexpression. GO analysis indicated that the upregulated genes were primarily related to the immune response. KEGG pathway enrichment analysis showed that immune signaling pathways, including the TNF, NF-κB, and chemokine signaling pathways, were significantly activated by NIK overexpression in aTC1-6 cells, while genes related to metabolism-associated signal pathways were significantly decreased. NIK(KA), the dominant-negative mutant of NIK, does not affect gene expression in aTC1-6 cells.
2018-12-30 | GSE112511 | GEO
Project description:Our findings establish NIK as a pivotal regulator of T cell metabolism in anti-tumor immunity and highlight a posttranslational mechanism of metabolic regulation involving the G6PD-NADPH redox system. CoIP assays revealed a strong physical interaction between NIK and G6PD in both T cells and transiently transfected 293 cells, suggesting G6PD to be a direct target of NIK. Using a phosphoprotein gel analysis approach, we demonstrated that NIK expression stimulated G6PD phosphorylation. To further study the mechanism, we performed mass spectrometry identify phosphorylation sites of G6PD stimulated by NIK
2020-10-05 | PXD020943 | Pride