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Specific Transcription Factors (specific + transcription_factor)
Selected AbstractsProstate cancer expression of runt-domain transcription factor Runx2, a key regulator of osteoblast differentiation and functionTHE PROSTATE, Issue 1 2003Kristen D. Brubaker Abstract BACKGROUND Prostate cancer (CaP) bone metastases express numerous proteins associated with bone cells. Specific transcription factors, including Runx2, regulate the expression of many bone-related factors in osteoblasts. Expression of these transcription factors in CaP may be linked to the ability of CaP bone metastases to influence bone remodeling. METHODS CaP tissues and cell lines were analyzed for expression of Runx2 mRNA by RT-PCR and in situ hybridization, and protein by immunohistochemistry, Western blotting, and electrophoretic mobility shift assays (EMSA). RESULTS Runx2 mRNA and protein were detected in CaP tissues and cell lines. A specific Runx2: OSE2 complex could be formed with PC-3 nuclear extracts. CONCLUSIONS Expression of Runx2 in CaP may be the molecular switch that is associated with expression of various bone-specific factors in CaP. In turn, expression of these factors can influence bone remodeling and possibly play a role in the growth and survival of CaP in bone. Prostate 56: 13,22, 2003. © 2003 Wiley-Liss, Inc. [source] Exploring the mast cell enigma: a personal reflection of what remains to be doneEXPERIMENTAL DERMATOLOGY, Issue 2 2008Beate M. Henz Abstract: Mast cells are traditionally viewed as effector cells of allergic reactions and parasitic diseases, but their importance in host defense against bacteria, in tissue remodelling, their bone marrow and stem cell origin and a central role of the stem cell factor (SCF) as mast cell growth and chemotactic factor has been worked out only in recent years. Despite this, major aspects about the nature of the cells and their role in disease remain unclear. This holds in particular for the identification of mast cell precursors and the role of growth factors that stimulate specific mast cell commitment from stem cells, such as nerve growth factor, neutrotrophin-3 and certain interleukins, alone and during interaction with SCF. Early data suggesting also an involvement of specific transcription factors need to be expanded in this process. Furthermore, although mast cell proliferative disease (mastocytosis) has been shown to be often associated with SCF receptor c-kit mutations, reasons for the development of this disease remain unclear. This holds also for mast cell release mechanisms in many types of mast cell-dependent urticaria. Exciting new insights are emerging regarding the role of mast cells in bacterial infections, in defense against tumors, in wound healing and in the interplay with the nervous system, with hormones, and in the neurohormonal network. The aim of this reflection is to delineate the many known and unknown aspects of mast cells, with a special focus on their development, and to discuss in detail two mast cell-related diseases, namely mastocytosis and urticaria. [source] Integrative nuclear FGFR1 signaling (INFS) as a part of a universal "feed-forward-and-gate" signaling module that controls cell growth and differentiationJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2003Michal K. Stachowiak Abstract A novel signaling mechanism is described through which extracellular signals and intracellular signaling pathways regulate proliferation, growth, differentiation, and other functions of cells in the nervous system. Upon cell stimulation, fibroblast growth factor receptor-1 (FGFR1), a typically plasma membrane-associated protein, is released from ER membranes into the cytosol and translocates to the cell nucleus by an importin-,-mediated transport pathway along with its ligand, FGF-2. The nuclear accumulation of FGFR1 is activated by changes in cell contacts and by stimulation of cells with growth factors, neurotransmitters and hormones as well as by a variety of different second messengers and thus was named integrative nuclear FGFR1 signaling (INFS). In the nucleus, FGFR1 localizes specifically within nuclear matrix-attached speckle-domains, which are known to be sites for RNA Pol II-mediated transcription and co-transcriptional pre-mRNA processing. In these domains, nuclear FGFR1 colocalizes with RNA transcription sites, splicing factors, modified histones, phosphorylated RNA Pol II, and signaling kinases. Within the nucleus, FGFR1 serves as a general transcriptional regulator, as indicated by its association with the majority of active nuclear centers of RNA synthesis and processing, by the ability of nuclear FGFR1 to activate structurally distinct genes located on different chromosomes and by its stimulation of multi-gene programs for cell growth and differentiation. We propose that FGFR1 is part of a universal "feed-forward-and-gate" signaling module in which classical signaling cascades initiated by specific membrane receptors transmit signals to sequence specific transcription factors (ssTFs), while INFS elicited by the same stimuli feeds the signal forward to the common coactivator, CREB-binding protein (CBP). Activation of CBP by INFS, along with the activation of ssTFs by classical signaling cascades brings about coordinated responses from structurally different genes located at different genomic loci. © 2003 Wiley-Liss, Inc. [source] Regulation of mitogen-activated protein kinases by glutamate receptorsJOURNAL OF NEUROCHEMISTRY, Issue 1 2007John Q. Wang Abstract Glutamate receptors regulate gene expression in neurons by activating intracellular signaling cascades that phosphorylate transcription factors within the nucleus. The mitogen-activated protein kinase (MAPK) cascade is one of the best characterized cascades in this regulatory process. The Ca2+ -permeable ionotropic glutamate receptor, mainly the NMDA receptor subtype, activates MAPKs through a biochemical route involving the Ca2+ -sensitive Ras-guanine nucleotide releasing factor, Ca2+/calmodulin-dependent protein kinase II, and phosphoinositide 3-kinase. The metabotropic glutamate receptor (mGluR), however, activates MAPKs primarily through a Ca2+ -insensitve pathway involving the transactivation of receptor tyrosine kinases. The adaptor protein Homer also plays a role in this process. As an information superhighway between surface glutamate receptors and transcription factors in the nucleus, active MAPKs phosphorylate specific transcription factors (Elk-1 and CREB), and thereby regulate distinct programs of gene expression. The regulated gene expression contributes to the development of multiple forms of synaptic plasticity related to long-lasting changes in memory function and addictive properties of drugs of abuse. This review, by focusing on new data from recent years, discusses the signaling mechanisms by which different types of glutamate receptors activate MAPKs, features of each MAPK cascade in regulating gene expression, and the importance of glutamate/MAPK-dependent synaptic plasticity in memory and addiction. [source] Role of Th17 cells in human autoimmune arthritisARTHRITIS & RHEUMATISM, Issue 10 2010Jan Leipe Objective To delineate the role of Th17 cells in the pathogenesis of autoimmune arthritides. Methods Th17 cells were analyzed in well-defined homogeneous cohorts of patients with the prototypical autoimmune arthritides rheumatoid arthritis (RA) and psoriatic arthritis (PsA), grouped according to patients who had very early active RA (n = 36; mean disease duration 2.8 months, Disease Activity Score in 28 joints 5.0) and those who had very early active PsA (n = 20; mean disease duration 2.3 months), none of whom had received treatment with glucocorticoids or disease-modifying antirheumatic drugs, as well as patients with established RA (n = 21; mean disease duration 68 months) who were considered either responders or nonresponders to therapy. Groups of healthy individuals and patients with osteoarthritis (a noninflammatory arthritis) were used as control cohorts. Expression of T lineage,specific transcription factors (RORC, T-bet, GATA-3, and FoxP3) and the response of CD4 T cells to Th17 cell,inducing conditions were analyzed in vitro. Results The frequencies of Th17 cells and levels of interleukin-17 strongly correlated with systemic disease activity at both the onset and the progression of RA or PsA. The values were reduced to control levels in patients with treatment-controlled disease activity. Th17 cells were enriched in the joints, and increased frequencies of synovial Th17 cells expressed CCR4 and CCR6, indicative of selective migration of Th17 cells to the joints. The intrinsically elevated expression of RORC, accompanied by biased Th17 cell development, and the resistance of Th17 cells to a natural cytokine antagonist in patients with RA and patients with PsA were suggestive of the underlying molecular mechanisms of uncontrolled Th17 activity in these patients. Conclusion Th17 cells play an important role in inflammation in human autoimmune arthritides, both at the onset and in established disease. [source] Interleukin-23 promotes Th17 differentiation by inhibiting T-bet and FoxP3 and is required for elevation of interleukin-22, but not interleukin-21, in autoimmune experimental arthritisARTHRITIS & RHEUMATISM, Issue 4 2010Adriana M. C. Mus Objective To examine the role of interleukin-23 (IL-23) in subgroup polarization of IL-17A,positive and/or interferon-, (IFN,),positive T cells in autoimmune disease,prone DBA/1 mice with and without collagen-induced arthritis. Methods A magnetic-activated cell sorting system was used to isolate CD4+ T cells from the spleen of naive and type II collagen (CII),immunized DBA/1 mice. These CD4+ T cells were stimulated in vitro under Th0, Th1, or different Th17 culture conditions. Intracellular staining for IL-17A and IFN, was evaluated by flow cytometry. In addition, Th17 cytokines and T helper,specific transcription factors were analyzed by enzyme-linked immunosorbent assay and/or quantitative polymerase chain reaction. Results In CD4+ T cells from naive DBA/1 mice, IL-23 alone hardly induced retinoic acid,related orphan receptor ,t (ROR,t), Th17 polarization, and Th17 cytokines, but it inhibited T-bet expression. In contrast, transforming growth factor ,1 (TGF,1)/IL-6 was a potent inducer of ROR,t, ROR,, IL-17A, IL-17F, IL-21, and FoxP3 in these cells. In contrast to TGF,1/IL-6, IL-23 was critical for the induction of IL-22 in CD4+ T cells from both naive and CII-immunized DBA/1 mice. Consistent with these findings, IL-23 showed a more pronounced induction of the IL-17A+IFN,, subset in CD4+ T cells from CII-immunized mice. However, in CD4+ T cells from naive mice, IL-23 significantly increased the TGF,1/IL-6,induced Th17 polarization, including elevated levels of IL-17A and IL-17F and decreased expression of T-bet and FoxP3. Of note, the IL-23,induced increase in IL-17A and IL-17F levels was prevented in T-bet,deficient mice. Conclusion IL-23 promotes Th17 differentiation by inhibiting T-bet and FoxP3 and is required for elevation of IL-22, but not IL-21, levels in autoimmune arthritis. These data indicate different mechanisms for IL-23 and TGF,1/IL-6 at the transcription factor level during Th17 differentiation in autoimmune experimental arthritis. [source] The two faces of short-range evolutionary dynamics of regulatory modes in bacterial transcriptional regulatory networksBIOESSAYS, Issue 7 2007S. Balaji Studies on the conservation of the inferred transcriptional regulatory network of prokaryotes have suggested that specific transcription factors are less-widely conserved in comparison to their target genes. This observation implied that, at large evolutionary distances, the turnover of specific transcription factors through loss and non-orthologous displacement might be a major factor in the adaptive radiation of prokaryotes. However, the recent work of Hershberg and Margalit1 suggests that, at shorter phylogenetic scales, the evolutionary dynamics of the bacterial transcriptional regulatory network might exhibit distinct patterns. The authors find previously unnoticed relationships between the regulatory mode (activation or repression), the number of regulatory interactions and their conservation patterns in ,-proteobacteria. These relationships might be shaped by the differences in the adaptive value and mode of operation of different regulatory interactions. BioEssays 29:625,629, 2007. © 2007 Wiley Periodicals, Inc. [source] | |||||||||||||