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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
12 Aug 1994-Science
TL;DR: The anti-inflammatory drugs sodium salicylate and aspirin inhibited the activation of NF-kappa B, which further explains the mechanism of action of these drugs.
Abstract: The transcription factor nuclear factor-kappa B (NF-kappa B) is critical for the inducible expression of multiple cellular and viral genes involved in inflammation and infection including interleukin-1 (IL-1), IL-6, and adhesion molecules. The anti-inflammatory drugs sodium salicylate and aspirin inhibited the activation of NF-kappa B, which further explains the mechanism of action of these drugs. This inhibition prevented the degradation of the NF-kappa B inhibitor, I kappa B, and therefore NF-kappa B was retained in the cytosol. Sodium salicylate and aspirin also inhibited NF-kappa B-dependent transcription from the Ig kappa enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells.

1,771 citations

Journal ArticleDOI
06 Aug 2010-Cell
TL;DR: A model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulate their localization to sets of previously active genes is proposed.

1,768 citations

Journal ArticleDOI
TL;DR: Conditional mutagenesis of Gr in the nervous system provides genetic evidence for the importance of Gr signalling in emotional behaviour because mutant animals show an impaired behavioural response to stress and display reduced anxiety.
Abstract: The glucocorticoid receptor (Gr, encoded by the gene Grl1) controls transcription of target genes both directly by interaction with DNA regulatory elements and indirectly by cross-talk with other transcription factors. In response to various stimuli, including stress, glucocorticoids coordinate metabolic, endocrine, immune and nervous system responses and ensure an adequate profile of transcription. In the brain, Gr has been proposed to modulate emotional behaviour, cognitive functions and addictive states. Previously, these aspects were not studied in the absence of functional Gr because inactivation of Grl1 in mice causes lethality at birth (F.T., C.K. and G.S., unpublished data). Therefore, we generated tissue-specific mutations of this gene using the Cre/loxP -recombination system. This allowed us to generate viable adult mice with loss of Gr function in selected tissues. Loss of Gr function in the nervous system impairs hypothalamus-pituitary-adrenal (HPA)-axis regulation, resulting in increased glucocorticoid (GC) levels that lead to symptoms reminiscent of those observed in Cushing syndrome. Conditional mutagenesis of Gr in the nervous system provides genetic evidence for the importance of Gr signalling in emotional behaviour because mutant animals show an impaired behavioural response to stress and display reduced anxiety.

1,754 citations

Journal ArticleDOI
05 Aug 2004-Nature
TL;DR: A novel ubiquitin ligase domain is defined and two sequential mechanisms by which A20 downregulates NF-κB signalling are identified, both of which participate in mediating a distinct regulatory effect.
Abstract: NF-kappaB transcription factors mediate the effects of pro-inflammatory cytokines such as tumour necrosis factor-alpha and interleukin-1beta. Failure to downregulate NF-kappaB transcriptional activity results in chronic inflammation and cell death, as observed in A20-deficient mice. A20 is a potent inhibitor of NF-kappaB signalling, but its mechanism of action is unknown. Here we show that A20 downregulates NF-kappaB signalling through the cooperative activity of its two ubiquitin-editing domains. The amino-terminal domain of A20, which is a de-ubiquitinating (DUB) enzyme of the OTU (ovarian tumour) family, removes lysine-63 (K63)-linked ubiquitin chains from receptor interacting protein (RIP), an essential mediator of the proximal TNF receptor 1 (TNFR1) signalling complex. The carboxy-terminal domain of A20, composed of seven C2/C2 zinc fingers, then functions as a ubiquitin ligase by polyubiquitinating RIP with K48-linked ubiquitin chains, thereby targeting RIP for proteasomal degradation. Here we define a novel ubiquitin ligase domain and identify two sequential mechanisms by which A20 downregulates NF-kappaB signalling. We also provide an example of a protein containing separate ubiquitin ligase and DUB domains, both of which participate in mediating a distinct regulatory effect.

1,749 citations

Journal ArticleDOI
TL;DR: The Jak-STAT pathway is the focus of this chapter, a novel mechanism in which cytosolic latent transcription factors, known as signal transducers and activators of transcription (STATs), are tyrosine phosphorylated by Janus family tyrosin kinases (Jaks), allowing STAT protein dimerization and nuclear translocation.
Abstract: Cytokines and interferons are molecules that play central roles in the regulation of a wide array of cellular functions in the lympho-hematopoietic system. These factors stimulate proliferation, differentiation, and survival signals, as well as specialized functions in host resistance to pathogens. Although cytokines are known to activate multiple signaling pathways that together mediate these important functions, one of these pathways, the Jak-STAT pathway, is the focus of this chapter. This pathway is triggered by both cytokines and interferons, and it very rapidly allows the transduction of an extracellular signal into the nucleus. The pathway uses a novel mechanism in which cytosolic latent transcription factors, known as signal transducers and activators of transcription (STATs), are tyrosine phosphorylated by Janus family tyrosine kinases (Jaks), allowing STAT protein dimerization and nuclear translocation. STATs then can modulate the expression of target genes. The basic biology of this system, including the range of known Jaks and STATs, is discussed, as are the defects in animals and humans lacking some of these signaling molecules.

1,749 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