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Journal ArticleDOI

Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins

TLDR
A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).
Abstract
Through the study of transcriptional activation in response to interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma), a previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that then phosphorylate substrate proteins called STATs (signal transducers and activators of transcription). The phosphorylated STAT proteins move to the nucleus, bind specific DNA elements, and direct transcription. Recognition of the molecules involved in the IFN-alpha and IFN-gamma pathway has led to discoveries that a number of STAT family members exist and that other polypeptide ligands also use the Jak-STAT molecules in signal transduction.

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Differentiation and gene expression profile of tumor-associated macrophages

TL;DR: Different tumor-environmental stimuli and signalling cascades involved in this switch in differentiation and the so connected gene regulation in TAMs are reviewed and therapeutic applications deducted from this differentiation and gene regulatory processes are presented.
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The IRF family of transcription factors: Inception, impact and implications in oncogenesis.

TL;DR: The regulation of oncogenesis by IRFs has important implications for understanding the host susceptibility to several Types of cancers, their progression, as well as the potential for therapeutic interventions.
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The lipopolysaccharide-binding protein is a secretory class 1 acute-phase protein whose gene is transcriptionally activated by APRF/STAT/3 and other cytokine-inducible nuclear proteins.

TL;DR: It is shown that induction of LBP expression is transcriptionally regulated and is dependent on stimulation with IL-1beta, IL-6, and dexamethasone, and unraveling of the mechanism of transcriptional activation of the LBP gene, involving three known transcription factors, may contribute to the understanding of the acute-phase response and the pathophysiology of sepsis and septic shock.
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Somatic and germline mutation in GRIM-19, a dual function gene involved in mitochondrial metabolism and cell death, is linked to mitochondrion-rich (Hürthle cell) tumours of the thyroid

TL;DR: The GRIM-19 mutations detected are the first nuclear gene mutations specific to Hürthle cell tumours to be reported to date and it is proposed that such mutations can be involved in the genesis of sporadic or familial Hurthlecell tumours through the dual function of GRim-19 in mitochondrial metabolism and cell death.
Journal ArticleDOI

How cells respond to interferons revisited: From early history to current complexity

TL;DR: The complex responses of cells to interferons are outlined, including the roles of kinases other than JAKs and transcription factors other than STATs, differential responses toInterferons alpha and beta, modulation of response by prior exposure to other cytokines ("priming"), cytokine-dependent induction of high level expression of STATs 1 and 3 and the activation of a new set of genes by these unphosphorylated STATs.
References
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Journal ArticleDOI

Stimulation of 3T3 cells induces transcription of the c- fos proto-oncogene

TL;DR: Transcription of the c-fos proto-oncogene is greatly increased within minutes of administering purified growth factors to quiescent 3T3 cells, and this stimulation is the most rapid transcriptional response to peptide growth factors yet described, implying a role for c- fos in cell-cycle control.
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Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis

TL;DR: Gel electrophoresis in studies of equilibrium binding, site distribution, and kinetics of protein-DNA interactions found that binding to the so-called third operator site (03) is 15-18 fold weaker than operator binding, and that the binding reactions with the first and third operators are uncoupled, implying that there is no communication between the sites.
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Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6

TL;DR: A new family member, Stat3, becomes activated through phosphorylation on tyrosine as a DNA binding protein in response to epidermal growth factor and interleukin-6 but not interferon gamma (IFN-gamma).
Journal ArticleDOI

SH2 and SH3 Domains: Elements that Control Interactions of Cytoplasmic Signaling Proteins

TL;DR: Observations suggest that SH2 and SH3 domains participate in the control of intracellular responses to growth factor stimulation.
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A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system

TL;DR: It is demonstrated that even when pre-formed in the presence of CAP-cAMP, the polymerase-promoter open complex becomes unstable if CAP is then selectively removed, and this gel method is applied to the study of the E. coli lactose operon regulatory system.
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