NLRP2, an Inhibitor of the NF-κB Pathway, Is Transcriptionally Activated by NF-κB and Exhibits a Nonfunctional Allelic Variant

Fontalba, Ana; Gutiérrez, Olga; Fernández-Luna, José L.

doi:10.4049/jimmunol.179.12.8519

Cited by 76 publications

(64 citation statements)

References 38 publications

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“…NALP2 mRNA was detected by RT-PCR to be expressed at low levels in HEK293T cells. Its expression is however upregulated by NF-κB activators (Fontalba et al, 2007). According to the UniGene profile, NALP4 is expressed at low levels in less than 10 tissues.…”

Section: Discussionmentioning

confidence: 99%

Screening of human gene promoter activities using transfected-cell arrays

Cheng

Guerasimova

Rosenstiel

et al. 2010

Gene

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Promoters are the best characterized transcriptional regulatory sequences in complex genomes because of their predictable location immediately upstream of transcription start sites. Despite a substantial body of literature describing transcriptional promoters, the identification of true start sites for all human transcripts is far from complete. The same is true of the key structural and functional elements responsible for promoter action in different cell types. In order to identify elements responsible for promoter activity, we applied transfected-cell array technology to functionally evaluate promoters for genes involved in inflammatory bowel disease. Seventy-four promoters were examined by reverse transfection of a promoter-fluorescent reporter constructs into a human embryonic kidney cell line (HEK293T). Sixteen (21.6%) promoters were found to be active in HEK293 T cells. Correlations between promoter activity and endogenous transcript level were calculated, and 75% of active promoters were found to be associated with transcriptional activity of their gene counterparts. These results provide experimental evidence of promoter activity, which may aid in understanding the regulation of gene expression. Moreover, this is the first large-scale functional study of regulatory sequences to use a high-throughput transfected-cell array technique.

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Section: Discussionmentioning

confidence: 99%

Screening of human gene promoter activities using transfected-cell arrays

Cheng

Guerasimova

Rosenstiel

et al. 2010

Gene

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“…Cell cultures from tissue specimens used in this study (GBM and mesenchymal stem-like cells) have been previously characterized and described by our group (8,13,14). The stem-like origin of the cells was tested by analyzing the patterns of differentiation just before their use (13,14).…”

Section: Primary Cell Culturesmentioning

confidence: 99%

Culture Dimensionality Influences the Resistance of Glioblastoma Stem-like Cells to Multikinase Inhibitors

Fernandez-Fuente

Mollinedo

Grande

et al. 2014

Molecular Cancer Therapeutics

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Sunitinib, an inhibitor of kinases, including VEGFR and platelet-derived growth factor receptor (PDGFR), efficiently induces apoptosis in vitro in glioblastoma (GBM) cells, but does not show any survival benefit in vivo.One detrimental aspect of current in vitro models is that they do not take into account the contribution of extrinsic factors to the cellular response to drug treatment. Here, we studied the effects of substrate properties including elasticity, dimensionality, and matrix composition on the response of GBM stem-like cells (GSC) to chemotherapeutic agents. Thirty-seven cell cultures, including GSCs, parenchymal GBM cells, and GBM cell lines, were treated with nine antitumor compounds. Contrary to the expected chemoresistance of GSCs, these cells were more sensitive to most agents than GBM parenchymal cells or GBM cell lines cultured on flat (twodimensional; 2D) plastic or collagen-coated surfaces. However, GSCs cultured in collagen-based threedimensional (3D) environments increased their resistance, particularly to receptor tyrosine kinase inhibitors, such as sunitinib, BIBF1120, and imatinib. Differences in substrate rigidity or matrix components did not modify the response of GSCs to the inhibitors. Moreover, the MEK-ERK and PI3K-Akt pathways, but not PDGFR, mediate at least in part, this dimensionality-dependent chemoresistance. These findings suggest that survival of GSCs on 2D substrates, but not in a 3D environment, relies on kinases that can be efficiently targeted by sunitinib-like inhibitors. Overall, our data may help explain the lack of correlation between in vitro and in vivo models used to study the therapeutic potential of kinase inhibitors, and provide a rationale for developing more robust drug screening models. Mol Cancer Ther; 13(6); 1664-72. Ó2014 AACR.

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“…Conversely, NLRP10 (that lacks an LRR domain) has been shown to be a negative regulator of the inflammasome (120) and an important initiator of adaptive immunity (58). NLRP2 and NLRP12 also appear to be negative regulators of immune response by interfering with NF-B activation (9,65,295). NLRP4, NLRP5, and NLPR7 have been reported to play roles in autophagy and in development (32,42,130,148), while NLRP9, NLRP11, and NLRP1 have been associated with autoimmune diseases in genetic studies (127,176,269).…”

Section: Nod1mentioning

confidence: 99%

NOD-Like Receptors: Versatile Cytosolic Sentinels

Motta

Soares

Sun

et al. 2015

Physiological Reviews

275

206

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Nucleotide binding oligomerization domain (NOD)-like receptors are cytoplasmic pattern-recognition receptors that together with RIG-I-like receptor (retinoic acid-inducible gene 1), Toll-like receptor (TLR), and C-type lectin families make up the innate pathogen pattern recognition system. There are 22 members of NLRs in humans, 34 in mice, and even a larger number in some invertebrates like sea urchins, which contain more than 200 receptors. Although initially described to respond to intracellular pathogens, NLRs have been shown to play important roles in distinct biological processes ranging from regulation of antigen presentation, sensing metabolic changes in the cell, modulation of inflammation, embryo development, cell death, and differentiation of the adaptive immune response. The diversity among NLR receptors is derived from ligand specificity conferred by the leucine-rich repeats and an NH2-terminal effector domain that triggers the activation of different biological pathways. Here, we describe NLR genes associated with different biological processes and the molecular mechanisms underlying their function. Furthermore, we discuss mutations in NLR genes that have been associated with human diseases.

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NLRP2, an Inhibitor of the NF-κB Pathway, Is Transcriptionally Activated by NF-κB and Exhibits a Nonfunctional Allelic Variant

Cited by 76 publications

References 38 publications

Screening of human gene promoter activities using transfected-cell arrays

Screening of human gene promoter activities using transfected-cell arrays

Culture Dimensionality Influences the Resistance of Glioblastoma Stem-like Cells to Multikinase Inhibitors

NOD-Like Receptors: Versatile Cytosolic Sentinels

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