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

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