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Transcription factor

About: Transcription factor is a research topic. Over the lifetime, 82881 publications have been published within this topic receiving 5400448 citations. The topic is also known as: transcription factors.


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Journal ArticleDOI
TL;DR: Data from a PCR-based technique and in situ hybridization revealed that while c-jun was induced in most neurons, c-fos induction was restricted to neurons undergoing chromatin condensation, a hallmark of apoptosis, and these data may outline a genetic program responsible for neuronal programmed cell death.
Abstract: We have examined the hypothesis that neuronal programmed cell death requires a genetic program; we used a model wherein rat sympathetic neurons maintained in vitro are deprived of NGF and subsequently undergo apoptosis. To evaluate gene expression potentially necessary for this process, we used a PCR-based technique and in situ hybridization; patterns of general gene repression and selective gene induction were identified in NGF-deprived neurons. A temporal cascade of induced genes included "immediate early genes," which were remarkable in that their induction occurred hours after the initial stimulus of NGF removal and the synthesis of some required ongoing protein synthesis. The cascade also included the cell cycle gene c-myb and the genes encoding the extracellular matrix proteases transin and collagenase. Concurrent in situ hybridization and nuclear staining revealed that while c-jun was induced in most neurons, c-fos induction was restricted to neurons undergoing chromatin condensation, a hallmark of apoptosis. To evaluate the functional role of the proteins encoded by these genes, neutralizing antibodies were injected into neurons. Antibodies specific for either c-Jun or the Fos family (c-Fos, Fos B, Fra-1, and Fra-2) protected NGF-deprived neurons from apoptosis, whereas antibodies specific for Jun B, Jun D, or three nonimmune antibody preparations had no protective effect. Because these induced genes encode proteins ranging from a transcription factor necessary for death to proteases likely involved in tissue remodeling concurrent with death, these data may outline a genetic program responsible for neuronal programmed cell death.

853 citations

Journal ArticleDOI
TL;DR: During progression and metastasis, tumor cells adapt to oxidative stress by increasing NADPH in various ways, including activation of AMPK, the PPP, and reductive glutamine and folate metabolism.

852 citations

Journal ArticleDOI
18 Mar 1994-Science
TL;DR: Macrophages from mice with a targeted disruption of the IFN regulatory factor-1 (IRF-1) gene produced little or no NO and synthesized barely detectable iNOS messenger RNA in response to stimulation, and infection with Mycobacterium bovis was more severe in IRf-1-/- mice than in wild-type mice.
Abstract: Production of nitric oxide (NO) by macrophages is important for the killing of intracellular infectious agents Interferon (IFN)-gamma and lipopolysaccharide stimulate NO production by transcriptionally up-regulating the inducible NO synthase (iNOS) Macrophages from mice with a targeted disruption of the IFN regulatory factor-1 (IRF-1) gene (IRF-1-/- mice) produced little or no NO and synthesized barely detectable iNOS messenger RNA in response to stimulation Two adjacent IRF-1 response elements were identified in the iNOS promoter Infection with Mycobacterium bovis (BCG) was more severe in IRF-1-/- mice than in wild-type mice Thus, IRF-1 is essential for iNOS activation in murine macrophages

851 citations

Journal ArticleDOI
TL;DR: Evidence is considered of the evidence implicating Stat proteins, particularly Stats 1, 3, and 5, in tumor formation and progression and the role of this protein in a number of biological functions had to be determined in conditional knockouts.
Abstract: The discovery of Stat proteins’ key role in IFN signaling, initially described over ten years ago, provided the first molecular link of growth factor receptor stimulation to the direct activation of a transcription factor (1). Since that time a large number of growth factor receptors and some nonreceptor tyrosine kinases have been found to lead to the activation of these transcription factors (2). The contributions of individual Stat proteins to normal cytokine signaling and development have been studied in various cell culture systems and in vivo in mice made deficient for one or more of these proteins (3). This approach has identified some related roles, as well as many unique, nonoverlapping physiological roles, for the various members of the Stat family. In summary, Stat1-deficient mice are unable to respond to IFNs and are subsequently susceptible to bacterial and viral pathogens. Likewise, disruption of Stat2 gives rise to animals unable to respond to type 1 IFNs, with increased susceptibility to viral infections (see Candotti et al., this Perspective series, ref. 4). Stat4- and Stat6-deficient animals reveal a requirement for IL-12– or IL-4–mediated proliferation of T cells, respectively (see Decker et al., this series, ref. 5). The phenotypes of Stat5A and Stat5B individual knockouts reveal the importance of Stat5A in breast development and lactation and the importance of Stat5B in the development of sexually dimorphic patterns of gene expression within the liver. In addition to these phenotypes, Stat5A/5B double knockouts are abnormal in their T cell and B cell development. Because Stat3-deficient animals die early in embryogenesis, the role of this protein in a number of biological functions had to be determined in conditional knockouts. As discussed by Levy and Lee in this series (6), Stat3 is implicated in keratinocyte migration, T cell apoptosis, IL-10–mediated signaling in macrophages, and the induction of apoptosis in the involuting breast. Beyond these various roles in normal cellular and physiological processes, the Stat proteins are now known to participate in cellular transformation and oncogenesis. Here, I consider the evidence implicating these molecules, particularly Stats 1, 3, and 5, in tumor formation and progression.

851 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20234,678
20226,545
20213,663
20203,530
20193,362
20183,288