Navigation Links
Critical link in cell death pathway revealed
Date:7/22/2009

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 today 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.


'/>"/>

Contact: Penny Fannin
fannin@wehi.edu.au
61-393-452-345
Walter and Eliza Hall Institute
Source:Eurekalert  

Related medicine news :

1. Flexi-Seal(R) Fecal Management System Receives 2008 Critical Care Nurse Advertising Effectiveness Award
2. Critical Access Hospital Consolidator Seeks Cost-Management Solutions with Broadlane
3. Emdeon To Collaborate With Rx Response in Critical Pharmacy Disaster Reporting
4. ICU Medical, Inc. to Acquire Hospiras Critical Care Product Line
5. MDS Nordion Continues to Urge Government of Canada to Complete MAPLE Project to Address Critical Medical Isotope Shortage
6. IBM Award for Innovative Solution to Tackling Worlds Most Critical Social and Environmental Problems
7. Parents Guide to Cord Blood Foundation Introduces New Brochure During Cord Blood Awareness Month to Address Critical Education Gap
8. Delirium in hospitalized adults: Situation critical, no relief available
9. Specialty Hospitals of America Accepts First Patients in New Long Term Critical Care Hospital Located in South East Washington
10. Pivotal White Paper Examines Retail Industrys Critical Role in Reengineering the Health Care System
11. Top Obama Administration Officials to Engage Latino Leaders on Critical Policy Issues in Los Angeles This Week
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Critical link in cell death pathway revealed
(Date:3/24/2017)... ... March 24, 2017 , ... Mlynarek Insurance ... to families and business owners across eastern Michigan, is connecting with the Oxford/Orion ... with financial difficulties. , The Oxford/Orion FISH Food Pantry works to ensure homeless, ...
(Date:3/24/2017)... Pittsburgh, PA (PRWEB) , ... March 24, 2017 ... ... the Oncology Nursing Society (ONS) wanted to create a communications platform that positions ... realize this goal, Elliance and ONS reinvented their online publication as an always-on, ...
(Date:3/24/2017)... ... 2017 , ... The law firm of Enea, Scanlan & Sirignano, LLP, ... resident Lauren C. Enea has joined the firm as an associate attorney. Ms. Enea, ... in elder law, Medicaid planning and applications, and Wills, Trusts and Estates. Samantha ...
(Date:3/24/2017)... , ... March 24, 2017 , ... ... year of enhancements, upgrading their training and leads programs. , In February, 2017, ... for elite sales agents, Performance Partners is designed to teach how to maximize ...
(Date:3/24/2017)... ... ... “End Time GPS”: a dauntless and enlightened study of the second-coming ... the creation of published author, Wesley Gerboth, a World War II veteran, with a ... Now, at age ninety-one, he shares the Wisdom God bestowed upon him in this ...
Breaking Medicine News(10 mins):
(Date:3/24/2017)... Oregon and PUNE, India , March 24, 2017 /PRNewswire/ ... 2015, and is estimated to reach $2,614 million by 2022, Globally, registering a CAGR ... to generate the highest revenue, and is projected to dominate the market during the ... ... Allied Market Research Logo ...
(Date:3/24/2017)... , March 24, 2017  Zymo Research ... and Hamilton Robotics, Inc., who designs, manufactures ... ongoing collaboration that teams Zymo Research,s DNA ... and DNA extraction products with Hamilton,s high-throughput ... optimized methods for microbiomics and RNA isolation ...
(Date:3/24/2017)... Research and Markets has announced the addition of the "Dental Implants ... ... for Dental Implants in US$ Million. The report provides separate comprehensive analytics ... , Europe , Asia-Pacific , ... Annual estimates and forecasts are provided for the period 2015 through 2022. ...
Breaking Medicine Technology: