Featured Research

from universities, journals, and other organizations

Critical Link In Cell Death Pathway Revealed

Date:
August 4, 2009
Source:
Walter and Eliza Hall Institute
Summary:
The role of a protein called XIAP in the regulation of cell death has been identified by researchers and has led them to recommend caution when drugs called IAP inhibitors are used to treat cancer patients with underlying liver conditions.

The role of a protein called XIAP in the regulation of cell death has been identified by Walter and Eliza Hall Institute researchers and has led them to recommend caution when drugs called IAP inhibitors are used to treat cancer patients with underlying liver conditions.

A team led by Professor Andreas Strasser from the institute's Molecular Genetics of Cancer division has found that XIAP (X-chromosome-linked inhibitor of apoptosis protein) is the critical factor that determines which of two pathways will be followed to culminate in a cell's death.

Programmed cell death (also called apoptosis) removes unwanted and dangerous cells from our bodies, protecting us against cancer development and diseases where the immune system attacks the body's own tissues, such as in insulin-dependent diabetes.

This cell death process is activated by proteins on the surface of cells. The most prominent of these cell surface proteins is FAS, but curiously it does not always activate apoptosis the same way, Professor Strasser said. "One of the things that's very curious about FAS is that, depending on the cell type, the way the killing of the cell happens is substantially different," he said.

"In so-called type I cells, such as lymphocytes (white blood cells involved in the immune response), the killing is very direct. When FAS is activated a protein-destroying enzyme called caspase-8 is recruited and activated, leading to activation of other enzymes (effector caspases) and rapid cell demolition," Professor Strasser said.

"But in so-called type II cells, which include hepatocytes (liver cells) and pancreatic β-cells (the cells that produce insulin), that direct pathway is not sufficient to kill the cells; amplification of the apoptosis signalling pathway is required."

Professor Strasser, with Drs Philipp Jost and Thomas Kaufmann (a former post-doctoral researcher from the institute who is now running his own lab in Bern, Switzerland) as well as with colleagues from St Vincent's Institute of Medical Research, LaTrobe University and the Institute of Molecular Medicine and Cell Research in Germany, has found that the protein XIAP is the discriminating factor between type I and type II FAS-induced cell death signaling.

The research has been published July 22 in the international journal Nature.

For death to occur in type II cells, caspase-8 must activate the death-promoting protein called BID. Without this activation of BID the cells don't die.

But the experiments of Professor Strasser's team revealed that when the gene that produces XIAP is turned off or if the XIAP protein is pharmacologically blocked, hepatocytes or pancreatic β-cells (both type II cells) will die in a type I manner; that is: independent of the presence of BID.

Professor Strasser said that the finding had implications for cancer patients with underlying liver conditions who were being treated with IAP inhibitors. These inhibitors would block the production of XIAP, thereby interfering with the normal cell death pathway for liver cells and increasing the likelihood of healthy liver cells being killed, he said.

The research would also be of interest to gastroenterologists as in several chronic liver diseases activation of FAS is thought to contribute to cell destruction, he said.


Story Source:

The above story is based on materials provided by Walter and Eliza Hall Institute. Note: Materials may be edited for content and length.


Cite This Page:

Walter and Eliza Hall Institute. "Critical Link In Cell Death Pathway Revealed." ScienceDaily. ScienceDaily, 4 August 2009. <www.sciencedaily.com/releases/2009/07/090722142834.htm>.
Walter and Eliza Hall Institute. (2009, August 4). Critical Link In Cell Death Pathway Revealed. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2009/07/090722142834.htm
Walter and Eliza Hall Institute. "Critical Link In Cell Death Pathway Revealed." ScienceDaily. www.sciencedaily.com/releases/2009/07/090722142834.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins