Navigation Links
Key protein regulating inflammation may prove relevant to controlling sepsis
Date:5/14/2009

Scientists at Singapore's Institute of Molecular and Cell Biology (IMCB), under the Agency for Science, Technology and Research (A*STAR), have identified the protein, WIP1, as the molecular "brake" that curbs severe inflammation in the body.

The findings may prove relevant to developing more effective treatments against sepsis, the severe inflammatory condition caused by bacterial infection that afflicts many patients in intensive care units (ICU).

In their paper, "WIP1 phosphatase is a negative regulator of NFκB signaling," published in the May 2009 issue of Nature Cell Biology (NCB), the IMCB scientists described their results showing the importance of WIP1 as an effective suppressor of inflammation and explained how the body was able to cope with an excess of inflammation brought on by the hyperactivation of the NFκB protein complex, is a signaling molecule that plays a key role in triggering inflammation.

"We have shown that WIP1 plays a critical role in suppressing the activity of NFκB and keeping NFκB levels within a safe range," said IMCB principal investigator Vinay Tergaonkar, Ph.D., who headed the research team. "In doing so, WIP1 minimizes the extent of inflammatory response that could lead to septic shock and subsequent death of patients."

Dr. Tergaonkar and his colleagues compared the inflammatory response in mice lacking in WIP1 and in a control group of mice with normal WIP1 levels. The inflammatory response was higher in the WIP1 deficient animals. Correspondingly, the inflammatory response in mice with high WIP1 levels was suppressed.

In separate research, a second group of scientists led by Dr. Tergaonkar found further evidence linking chronic inflammation to the development of cancers such as that of the stomach and liver.

Dr. Tergaonkar and his colleagues discovered that the kinase enzyme IκB kinase 2 (IKK2), which is known for causing inflammation through the activation of NFκB, is also responsible for "ordering" the destruction of the tumour suppressor protein p53.

This discovery, published in the February 2009 issue of the Proceedings of the National Academy of Sciences (PNAS) and entitled, "Phosphorylation of p53 by IκB kinase 2 promotes its degradation by β-TrCP," provides fresh insight about how cells that have become inflamed due to exposure to high IKK2 activity, can become more susceptible to tumour development.

"Our recent discoveries have provided an explanation on the beneficial and harmful effects of inflammation that have baffled scientists for years," added Dr Tergaonkar. "While the natural inflammatory response serves to help the body clear infection, excessive inflammation, on the other hand, promotes cellular changes that lead to the uncontrolled growth of cells that characterizes cancer and enables its spread. These new insights involving NFκB, WIP1 and IKK2 are fostering new anti-inflammatory therapeutic approaches to human ailments ranging from inflammation (like sepsis) to cancer."

Shen Han-Ming, Ph.D., an expert in cancer cell biology at the National University of Singapore's Yong Loo Lin School of Medicine, said, "Taken together, the work in Dr Tergaonkar's lab has significantly advanced our understanding of the regulatory mechanisms of NFκB and expanded the functional scope of NFκB. More important, such findings offer new opportunities for modulation of the NFκB signaling pathway and for exploring new therapeutic strategies in various human diseases such as cancer and sepsis."


'/>"/>

Contact: Cathy Yarbrough
sciencematter@yahoo.com
858-243-1814
Agency for Science, Technology and Research (A*STAR), Singapore
Source:Eurekalert

Related biology news :

1. Pliable proteins keep photosynthesis on the light path
2. Heart protein regulates blood vessel maintenance
3. EMBL scientists develop first fully automated pipeline for multiprotein complex production
4. Protein analysis methods, viral vectors featured in Cold Spring Harbor Protocols
5. Small molecules might block mutant protein production in Huntingtons disease
6. ISU researcher identifies key function in protein, cell transcription
7. Brain protein central to both Parkinsons, drug addiction identified
8. SUMO protein guides chromatin remodeler to suppress genes
9. New study reveals the protein that makes phosphate chains in yeast
10. Autopilot guides proteins in brain
11. New data on the breakdown of the KRas protein
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/6/2017)... Forecasts by Product Type (EAC), ... End-Use (Transportation & Logistics, Government & Public Sector, Utilities ... Generation Facility, Nuclear Power), Industrial, Retail, Business Organisation (BFSI), ... you looking for a definitive report on the $27.9bn ... ...
(Date:4/3/2017)... 2017  Data captured by IsoCode, IsoPlexis ... a statistically significant association between the potency ... and objective response of cancer patients post-treatment. ... whether cancer patients will respond to CAR-T ... as to improve both pre-infusion potency testing and ...
(Date:3/28/2017)... PUNE, India , March 28, 2017 ... (Analog, IP, Biometrics), Hardware (Camera, Monitors, Servers, Storage Devices), ... Maintenance), Vertical, and Region - Global Forecast to 2022", ... 30.37 Billion in 2016 and is projected to reach ... 15.4% between 2017 and 2022. The base year considered ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... ... October 12, 2017 , ... DuPont Pioneer and ... they have entered into a multiyear collaboration to identify and characterize novel CRISPR-Cas ... tools for gene editing across all applications. , Under the terms of the ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... analysis platform specifically designed for life science researchers to analyze and interpret ... Rosalind Franklin, who made a major contribution to the discovery of the ...
(Date:10/11/2017)... CA, USA (PRWEB) , ... October 11, 2017 , ... ... to take place on 7th and 8th June 2018 in San Francisco, CA. The ... influencers as well as several distinguished CEOs, board directors and government officials from around ...
(Date:10/11/2017)... ... 2017 , ... Disappearing forests and increased emissions are the main causes of ... year. Especially those living in larger cities are affected by air pollution related diseases. ... most pollution-affected countries globally - decided to take action. , “I knew I had ...
Breaking Biology Technology: