Navigation Links
A new signaling pathway of the immune system is elucidated
Date:3/31/2011

A new signaling pathway, which is important for the regulation of the immune response and inflammation, was discovered by an international team of scientists led by prof Ivan Dikic from the Goethe University, Frankfurt, Germany. The scientists studied the involvement of ubiquitin, a universally present signaling protein in the cell. In today's issue of the scientific journal "Nature" the scientists report a novel type of modified ubiquitin chains involved in regulation of various processes within the cell.

The researchers have shown that linear ubiquitin, where ubiquitin proteins are attached to each other in a head to tail fashion, regulates signaling cascades initiated by cytokine receptors at the cell membrane. Cytokines are essential for the proper immune response e. g. tumor necrosis factor (TNF-alpha) alpha is released mainly by the macrophages and plays an important role in local and body-wide inflammation.

When a cytokine docks on the receptor of a cell, it induces a signaling cascade in many cell types, which transmits a signal to the nucleus the DNA centre of the cell. After cytokine activation of its receptor, the linear ubiquitin ligase complex (LUBAC), which links ubiquitin into head-to-tail chains, is activated at the start of this cascade. This enzyme stimulates nuclear factor kappaB (NF-kappaB), which coordinates the expression of important genes for the immune response, including the production of antibodies. However, how the molecules of this cascade function in detail and which structures interact is still under investigation.

The Dikic group solved an integral part of this puzzle. Sharpin, a protein containing a Ubiquitin-like and Ubiquitin-binding domain (UBD), constitutes a key component of the linear Ubiquitin ligase complex. Using animal models, they show that a lack of Sharpin causes heavy inflammation of numerous organs and in particular the skin. This is characterized as chronic proliferative dermatitis with death of keratinocytes, the predominant cells of the epidermis in charge of protecting the skin against environmental damage. This effect is dependent on the TNF signaling pathways.

The research reported allows us to reshape our thinking about how chronic proliferative dermatitis arises in humans, as well as opening new avenues of therapeutic intervention in the TNF-alpha signalling pathway. Moreover, a potential source of this disease may arise from mutations in a critical region of the linear ubiquitin ligase complex (LUBAC) allowing identification of patients that may respond well to targeted therapy. "In patients suffering from chronic proliferative dermatitis with unclear origin, it is now possible to specifically look for a mutation in LUBAC components", suggests Ivan Dikic.


'/>"/>

Contact: Ivan Dikic
ivan.dikic@biochem2.de
49-696-301-5652
Goethe University Frankfurt
Source:Eurekalert

Related biology news :

1. Signaling path in brain may prevent that Im full message, UT Southwestern scientists discover
2. Nailing down a crucial plant signaling system
3. Carnegie Mellon researchers discover mechanism for signaling receptor recycling
4. Microfluidics-imaging platform detects cancer growth signaling in minute biopsy samples
5. Protein provides link between calcium signaling in excitable and non-excitable cells
6. Inhibiting cell signaling pathway may improve bone marrow transplant success rate
7. Investigators discover a new hot spot for the genesis of signaling neurons in the adult brain
8. New molecular signaling cascade increases glucose uptake
9. Scientists post lower speed limit for cell-signaling protein assembly
10. Insulin signaling key to caste development in bees
11. Cell signaling classification system gives researchers new tool
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/8/2017)... , Feb. 7, 2017 Report Highlights ... billion by 2021 from $8.3 billion in 2016 at ... 2016 to 2021. Report Includes - An overview ... global market trends, with data from 2015 and 2016, ... 2021. - Segmentation of the market on the basis ...
(Date:2/3/2017)... -- Texas Biomedical Research Institute announced that its Board of Trustees ... the Institute,s new President and CEO. Dr. Schlesinger will take ... is currently the Chair of the Department of Microbial Infection ... Biology at Ohio State University. "We are delighted ... of Texas Biomed," said Dr. James O. Rubin , ...
(Date:2/1/2017)... BOSTON, Massachusetts , February 1, 2017 ... and events on emerging technology, announces the availability of a new ... Continue Reading ... ... systems in industrial and collaborative robots. Source: IDTechEx Report "Sensors for ...
Breaking Biology News(10 mins):
(Date:2/24/2017)... 2017  Aethlon Medical, Inc. (Nasdaq: AEMD ... Chairman and CEO, Jim Joyce . ... last Saturday, Bill Gates warned world leaders ... than nuclear weapons. Mr. Gates expressed his concern, which ... that scientific terrorists have access to the necessary tools ...
(Date:2/24/2017)... Inc. (NASDAQ: CBPO) ("China Biologic" or the "Company"), a leading ... financial results for the fourth quarter and fiscal year of ... Total sales in the fourth quarter of ... 13.6% in USD terms to $77.6 million from $68.3 million ... profit increased by 13.3% to $46.8 million from $41.3 million ...
(Date:2/23/2017)... , ... February 23, 2017 , ... ... Discovery Services portfolio to include an array of biochemical analyses critical for ... data to drive their hit-to-lead and SAR programs, including inhibitor potency and selectivity, ...
(Date:2/23/2017)... Minn. , Feb. 23, 2017  Imanis ... new product line of oncolytic vaccinia viruses for ... Corporation as part of Genelux,s proprietary, vaccinia virus-based ... are excited to enter into a partnership with ... selected oncolytic vaccinia viruses for use in research," ...
Breaking Biology Technology: