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A paradigm shift in immune response regulation
Date:3/19/2009

Over the past decade various pieces of the puzzle how signal transmission controls immunity have been coming together. Now, in Cell an international team reports a paradigm shift in the regulation of immune response. Their results show that interaction with a linear ubiquitin chain is crucial for nuclear factor kappa B activation. Their findings may also contribute towards structure-based drug design to target the defective NF-κB pathway in diseases such as cancer, inflammation and immunodeficiency.

The body's first line of defence against bacteria and viruses is the innate immune system where phagocytes identify the foreign organism and initiate an alarm reaction, often accompanied by inflammation. As a consequence, molecular cues are produced in the blood, such as Tumor Receptor Factors (TNF) or interleukin-1, and these stimulate further reactions in the immune system. But what exactly happens after the molecular cues have docked onto the cell receptors that specialize in immune response? What is the basis of signal transmission from the cellular receptors into the cellular interior? Over the past decade, the overall picture of this large puzzle has been gradually pieced together to show that modifications in the cell protein - including the addition of phosphate groups (phosphorylation) or the conjugation of small modifier ubiquitin (ubiquitination) - play a central role in controlling the immune system.

Scientists at Frankfurt's Goethe University led by Prof. Ivan Dikic have established an international collaboration to investigate the role of ubiquitin modification in these pathways. The international team includes the laboratories of Soichi Wakatsuki (Photon factory, Tsukuba, Japan), Fumiyo Ikeda (MedILS, Split, Croatia), Felix Randow (LMB, Cambridge, UK) and David Komander (LMB, Cambridge, UK). They have been investigating how a transcription factor known as the nuclear factor kappa-B (NF-κB) coordinates the gene ex
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Contact: Dr. Ivan Dikic
ivan.dikic@biochem2.de
49-696-301-4546
Goethe University Frankfurt
Source:Eurekalert

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