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Major Transcription Factors (major + transcription_factor)
Selected AbstractsTargeted Expression of SHH Affects Chondrocyte Differentiation, Growth Plate Organization, and Sox9 Expression,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2004Sara Tavella Abstract The role of Hedgehogs (Hh) in murine skeletal development was studied by overexpressing human Sonic Hedgehog (SHH) in chondrocytes of transgenic mice using the collagen II promoter/enhancer. Overexpression caused a lethal craniorachischisis with major alterations in long bones because of defects in chondrocyte differentiation. Introduction: Hedgehogs (Hhs) are a family of secreted polypeptides that play important roles in vertebrate development, controlling many critical steps of cell differentiation and patterning. Skeletal development is affected in many different ways by Hhs. Genetic defects and anomalies of Hhs signaling pathways cause severe abnormalities in the appendicular, axial, and cranial skeleton in man and other vertebrates. Materials and Methods: Genetic manipulation of mouse embryos was used to study in vivo the function of SHH in skeletal development. By DNA microinjection into pronuclei of fertilized oocytes, we have generated transgenic mice that express SHH specifically in chondrocytes using the cartilage-specific collagen II promoter/enhancer. Transgenic skeletal development was studied at different embryonic stages by histology. The expression pattern of specific chondrocyte molecules was studied by immunohistochemistry and in situ hybridization. Results: Transgenic mice died at birth with severe craniorachischisis and other skeletal defects in ribs, sternum, and long bones. Detailed analysis of long bones showed that chondrocyte differentiation was blocked at prehypertrophic stages, hindering endochondral ossification and trabecular bone formation, with specific defects in different limb segments. The growth plate was highly disorganized in the tibia and was completely absent in the femur and humerus, leading to skeletal elements entirely made of cartilage surrounded by a thin layer of bone. In this cartilage, chondrocytes maintained a columnar organization that was perpendicular to the bone longitudinal axis and directed toward its outer surface. The expression of SHH receptor, Patched-1 (Ptc1), was greatly increased in all cartilage, as well as the expression of parathyroid hormone-related protein (PTHrP) at the articular surface; while the expression of Indian Hedgehog (Ihh), another member of Hh family that controls the rate of chondrocyte maturation, was greatly reduced and restricted to the displaced chondrocyte columns. Transgenic mice also revealed the ability of SHH to upregulate the expression of Sox9, a major transcription factor implicated in chondrocyte-specific gene expression, in vivo and in vitro, acting through the proximal 6.8-kb-long Sox9 promoter. Conclusion: Transgenic mice show that continuous expression of SHH in chondrocytes interferes with cell differentiation and growth plate organization and induces high levels and diffuse expression of Sox9 in cartilaginous bones. [source] NF-,B in Photodynamic Therapy: Discrepancies of a Master RegulatorPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2006Jean-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] Rsp5 is required for the nuclear export of mRNA of HSF1 and MSN2/4 under stress conditions in Saccharomyces cerevisiaeGENES TO CELLS, Issue 2 2008Yutaka Haitani Rsp5 is an essential and multi-functional E3 ubiquitin ligase in Saccharomyces cerevisiae. We previously isolated the Ala401Glu rsp5 mutant that is hypersensitive to various stresses. In rsp5A401E cells, the transcription of the stress protein genes was defective. To understand the mechanism by which Rsp5 regulates the expression of stress proteins, we analyzed the expression and localization of two major transcription factors, Hsf1 and Msn2/4, required for stress protein gene expression in S. cerevisiae. The mRNA levels of HSF1 and MSN2/4 in rsp5A401E cells were slightly lower than those of wild-type cells. An interesting finding is that the protein levels of HSF1 and Msn2/4 were remarkably defective in rsp5A401E cells after exposure to temperature up-shift and ethanol, although these proteins are mainly localized in the nucleus under these stress conditions. We also showed that the mRNAs of HSF1 and MSN2/4 were accumulated in the nucleus of rsp5A401E cells after exposure to temperature up-shift and ethanol, and even under non-stress conditions, suggesting that Rsp5 is required for the nuclear export of these mRNAs. These results indicate that, in response to environmental stresses, Rsp5 primarily regulates the expression of Hsf1 and Msn2/4 at the post-transcriptional level and is involved in the repair system of stress-induced abnormal proteins. [source] Regulation of gene expression in osteoblastsBIOFACTORS, Issue 1 2010Eric D. Jensen Abstract In recent years, much progress has been made in understanding the factors that regulate the gene expression program that underlies the induction, proliferation, differentiation, and maturation of osteoblasts. A large and growing number of transcription factors make important contributions to the precise control of osteoblast formation and function. It has become increasingly clear that these diverse transcription factors and the signals that regulate their activity cannot be viewed as discrete, separate signaling pathways. Rather, they form a highly interconnected, cooperative network that permits gene expression to be closely regulated. There has also been a substantial increase in our understanding of the mechanistic control of gene expression by cofactors such as acetyltransferases and histone deacetylases. The purpose of this review is to highlight recent progress in understanding the major transcription factors and epigenetic coregulators, including histone deacetylases and microRNAs, involved in osteoblastogenesis and the mechanisms that determine their functions as regulators of gene expression. [source] Signal transduction of inflammatory cytokines and tumor developmentCANCER SCIENCE, Issue 6 2006Akihiko Yoshimura It has been estimated that >20% of all malignancies are initiated or exacerbated by inflammation. Until recently, the molecular basis of this process has not been clarified. However, recent studies have uncovered the molecular mechanism of intracellular signaling pathways of inflammatory cytokines such as tumor necrosis factor (TNF)-,, interferon (IFN)-, and interleukin (IL)-6. Three major transcription factors including NF-,B, STAT1 and STAT3 have been shown to play major roles in transmitting inflammatory cytokine signals to the nucleus. One function of NF-,B and STAT3 in tumor cells is the promotion of cell growth and cell survival through the induction of target genes, whose products promote cell division and inhibit apoptosis. In addition, NF-,B and STAT1 are important transcription factors that induce inflammatory mediators from inflammatory cells, especially macrophages, while STAT3 often antagonizes this process. STAT1 is generally believed to be an anti-oncogene because it promotes apoptosis through p53, but it could promote inflammation-mediated tumor development by enhancing tissue injury, remodeling, fibrosis and inflammation. Hence, the inhibition of NF-,B and STATs offers a strategy for treatment of a variety of malignancies and can convert inflammation-induced tumor growth into inflammation-induced tumor regression. (Cancer Sci 2006; 97) [source] | |||||||||||||