Figure 1. Negative feedback regulation of inflammatory responses. The transcription factor NF-êB activates transcription of its target genes, such as A20 and IêBá. Products of these genes function as negative regulators of NF-êB and limit the duration of its activation. This is desirable because persistent activation of NF-êB can lead to various pathogenic conditions such as chronic inflammation, autoimmune diseases, and cancer.
Figure 2. The role of DSIF in the control of inflammatory responses. Upon NF-êB activation, DSIF is recruited to the A20 and IêBá genes and contributes to the negative feedback regulation in a unique manner. DSIF facilitates the expression of these genes by stimulating capping, splicing, and export of their mRNAs. Otherwise, these steps are rate-limiting, and A20 and IêBá proteins are not synthesized successfully.
Activity of NF-êB is usually transient because products of these genes function as negative regulators of NF-êB, resulting in a negative feedback and limiting the duration of NF-êB activation (Figure 1). In certain diseases NF-êB activation becomes persistent, perhaps due to an interruption of this feedback loop.
NF-êB activation results in recruitment of the protein DSIF at the target genes A20 and IêBá. The researchers confirmed the role of DSIF in the negative feedback regulation of NF-êB activity by downregulating a protein subunit of DSIF and comparing the treated cells with controls. In untreated cells the levels of proteins for the target genes A20 and IêBá are high. Although the levels diminish significantly in 30 minutes following a process called TNF-á induction, which is caused by degradation of the proteins, within 2 hours the levels recover. In knockdown cells, however, the levels remained diminished 2 hours after TNF-á induction.
Further investigations using chromatin immunoprecipitation assays revealed abnormalities in the synthesis of A20 and IêBá proteins in the knock down cells. A significant portion of the A20 and IêBá mRNAs in the knockdown cells were uncapped and unspliced (Fig. 2).
The researchers also studied how export was affected in DSIF knockdown cells. Export of mature mRNAs from the nucleus to the cytoplasm is a highly regulated process incorporating quality assurance checks. The researchers prepared RNA from cytosolic and nuclear cell fractions for comparison. In knockdown cells following TNF-á induction, the nuclear fractions had much larger amounts of A20 and IêBá than the cytosolic fractions, suggesting accumulation in the nucleus.
The impact observed on the synthesis and export of A20 and IêBá in DSIF knockdown cells was striking. A20 and IêBá are also responsible for regulating other cell signalling processes and it is likely that the effects on associated signalling processes contribute to the overall impact of DSIF knockdown.
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23.03.2018 | Institut Pasteur
Scientists develop tiny tooth-mounted sensors that can track what you eat
22.03.2018 | Tufts University
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
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