B Transcription Factor (b + transcription_factor)

Distribution by Scientific Domains


Selected Abstracts


Synergistic activation of interferon-, gene transcription by the viral FLICE inhibitory protein of Kaposi's sarcoma-associated herpesvirus and type,I IFN activators

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2007
Nathalie Cloutier
Abstract Expression of Kaposi's sarcoma-associated herpesvirus v-FLIP leads to the spindle-shape morphology of endothelial cells and is essential for the survival of primary effusion lymphoma cells. Activation of the NF-,B transcription factor by v-FLIP is responsible for these effects. Considering that the interferon-, (ifn- ,) gene is regulated partly through NF-,B, we sought to determine whether v-FLIP would activate the expression of the ifn -, gene. Our results indicate that when v-FLIP is expressed by itself it has no effect on ifn -, gene activation but when it is combined with known IFN-, inducers, a synergistic activation of the ifn -, gene occurs. This effect is strictly dependent on NF-,B and is mediated through the positive regulatory domain,II of the IFN-, promoter. Furthermore, we report that protection from Fas-induced cell-death by v-FLIP is observed whether or not the type,I IFN signaling pathway is activated. Our work therefore contributes to increase our knowledge on v-FLIP, highlighting the complex immunomodulatory properties of this anti-apoptotic viral protein. [source]


NF-,B inhibition triggers death of imatinib-sensitive and imatinib-resistant chronic myeloid leukemia cells including T315I Bcr-Abl mutants

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2009
Nadia Lounnas
Abstract The Bcr-Abl inhibitor imatinib is the current first-line therapy for all newly diagnosed chronic myeloid leukemia (CML). Nevertheless, resistance to imatinib emerges as CML progresses to an acute deadly phase implying that physiopathologically relevant cellular targets should be validated to develop alternative therapeutic strategies. The NF-,B transcription factor that exerts pro-survival actions is found abnormally active in numerous hematologic malignancies. In the present study, using Bcr-Abl-transfected BaF murine cells, LAMA84 human CML cell line and primary CML, we show that NF-,B is active downstream of Bcr-Abl. Pharmacological blockade of NF-,B by the IKK2 inhibitor AS602868 prevented survival of BaF cells expressing either wild-type, M351T or T315I imatinib-resistant mutant forms of Bcr-Abl both in vitro and in vivo using a mouse xenograft model. AS602868 also affected the survival of LAMA84 cells and of an imatinib-resistant variant. Importantly, the IKK2 inhibitor strongly decreased in vitro survival and ability to form hematopoietic colonies of primary imatinib resistant CML cells including T315I cells. Our data strongly support the targeting of NF-,B as a promising new therapeutic opportunity for the treatment of imatinib resistant CML patients in particular in the case of T315I patients. The T315I mutation escapes all currently used Bcr-Abl inhibitors and is likely to become a major clinical problem as it is associated with a poor clinical outcome. 2009 UICC [source]


Non-conventional signal transduction by type 1 interferons: The NF-,B pathway

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2007
Ziyun Du
Abstract Type I interferons (IFNs) regulate diverse cellular functions by modulating the expression of IFN-stimulated genes (ISGs) through the activation of the well established signal transduction pathway of the Janus Kinase (JAK) and signal transducers and activators of transcription (STAT) proteins. Although the JAK,STAT signal transduction pathway is critical in mediating IFN's antiviral and antiproliferative activities, other signaling pathways are activated by IFNs and regulate cellular response to IFN. The NF-,B transcription factor regulates the expression of genes involved in cell survival and immune responses. We have identified a novel IFN mediated signal pathway that leads to NF-,B activation and demonstrate that a subset of ISGs that play key roles in cellular response to IFN is regulated by NF-,B. This review focuses on the IFN-induced NF-,B activation pathway and the role of NF-,B in ISG expression, antiviral activity and apoptosis, and the therapeutic application of IFN in cancer and infectious disease. J. Cell. Biochem. 102: 1087,1094, 2007. 2007 Wiley-Liss, Inc. [source]


Poster Sessions BP06: Neurogenesis, Stem Cells and Apoptosis

JOURNAL OF NEUROCHEMISTRY, Issue 2002
J. Qiu
The NF-,B transcription factor regulates bcl-x gene expression, which may determine hypoxia-induced neuronal apoptosis. We examined hypoxia-induced NF-,B and Bcl-xL changes in rat hippocampus. We showed differential hypoxia-induced NF-,B binding to the bcl-x promoter CS4 and IgG,,B enhancer sequences by rat hippocampal nuclear extracts. The differential NF-,B binding to these two promoter sequences was also determined in a contused spinal cord injury model and in vitro studies with LPS-treated Hela cells. There was tissue-, gene promoter-specific and time-dependent regulation of bcl-x gene expression by NF-,B in support of the hypothesis that NF-,B has tissue- and gene-specific regulatory effects and that these effects may account for both the pro- and anti-apoptotic roles assigned to NF-,B in different apoptotic processes. We applied ,decoy' oligonucleotides with sequences specific to different promoters to the rat hippocampus and measured ,decoy' inhibitory effects on nuclear NF-,B binding. The IgG-,B enhancer sequence ,decoy' showed stronger inhibition on nuclear NF-,B c-Rel/p50 binding to the bcl-x gene promoter CS4 sequence when compared to NF-,B p50/p50 binding to the same sequence. This result suggests that the ,decoy' approach has the potential to selectively manipulate NF-,B regulation of gene expression in response to hypoxia. Acknowledgements:, Supported by NINDS NS-39161, Shriner Grant 8710 and a Grant from the Sealy Center on Aging to J. Qiu. [source]


Genome-wide analysis of the general stress response in Bacillus subtilis

MOLECULAR MICROBIOLOGY, Issue 4 2001
Chester W. Price
Bacteria respond to diverse growth-limiting stresses by producing a large set of general stress proteins. In Bacillus subtilis and related Gram-positive pathogens, this response is governed by the ,B transcription factor. To establish the range of cellular functions associated with the general stress response, we compared the transcriptional profiles of wild and mutant strains under conditions that induce ,B activity. Macroarrays representing more than 3900 annotated reading frames of the B. subtilis genome were hybridized to 33P-labelled cDNA populations derived from (i) wild-type and sigB mutant strains that had been subjected to ethanol stress; and (ii) a strain in which ,B expression was controlled by an inducible promoter. On the basis of their significant ,B -dependent expression in three independent experiments, we identified 127 genes as prime candidates for members of the ,B regulon. Of these genes, 30 were known previously or inferred to be ,B dependent by other means. To assist in the analysis of the 97 new genes, we constructed hidden Markov models (HMM) that identified possible ,B recognition sequences preceding 21 of them. To test the HMM and to provide an independent validation of the hybridization experiments, we mapped the ,B -dependent messages for seven representative genes. For all seven, the 5, end of the message lay near typical ,B recognition sequences, and these had been predicted correctly by the HMM for five of the seven examples. Lastly, all 127 gene products were assigned to functional groups by considering their similarity to known proteins. Notably, products with a direct protective function were in the minority. Instead, the general stress response increased relative message levels for known or predicted regulatory proteins, for transporters controlling solute influx and efflux, including potential drug efflux pumps, and for products implicated in carbon metabolism, envelope function and macromolecular turnover. [source]


NF-,B in Photodynamic Therapy: Discrepancies of a Master Regulator

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2006
Jean-Yves Matroule
ABSTRACT Tumor eradication by photodynamic therapy (PDT) results from the onset of distinct killing processes. In addition to the well-known necrotic and apoptotic mechanisms, PDT initiates an inflammatory response that will indirectly contribute to tumor clearance. The NF-,B transcription factor is a major regulator of inflammation modulating the expression of cyto-kines, chemokines, and adhesion molecules in various cell types in response to a large number of stimuli. Besides, NF-,B regulates the expression of antiapoptotic genes, cyclooxygenases (COXs) and metalloproteinases (MMPs) as well, thereby favoring tumor cell proliferation and dissemination. In the present review, we aim to summarize the current knowledge on NF-,B status following photosensitization of cancer cells and endothelial cells. In order to unravel the NF-,B impact in PDT tumorigenicity and recurrences, we will stress the discrepancies of this major transcription factor relative to the signaling cascades underlying its activation and the cellular effects triggered by its translocation into the nucleus and its binding to its target genes. [source]