LIAI Scientists Discover Key Protein in Activating Cell Death;

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LIAI Scientists Discover Key Protein in Activating Cell Death;

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( BW)(CA-LA-JOLLA-INSTITUTE) LIAI Scientists Discover Key Protein in

Activating Cell Death; Research Could Lead to Future Advances in Cancer and

Autoimmune Therapies

Business Editors & Health/Medical Writers

SAN DIEGO--(BUSINESS WIRE)--June 11, 2004--Researchers at La Jolla

Institute for Allergy & Immunology (LIAI) have identified a key protein

(NDUSF1), which is an integral component of the pathway leading to

programmed cell death, a natural process of cell suicide which eliminates

excess or damaged cells. This finding may have important implications for

regulating cell death and could one day lead to the development of new

treatments or cures for some cancers and autoimmune diseases.

In a paper (Disruption of Mitochondrial Function During Apoptosis is

Mediated By Caspase Cleavage of NDUSF1), published today in the scientific

journal Cell, Doug Green, Ph.D., and a team of scientists that he led have

uncovered a key part of the mechanism by which the pathway leading to

apoptosis or programmed cell death is activated.

Because of previous research conducted, in part, by Green's lab,

scientists already knew that the mitochondria, the energy power plant of the

cell, triggers the proteins called caspases to kill the cell. In the latest

study, Green and his team found that the caspases accomplish this execution

by going back into the mitochondria and destroying one key protein (NDUSF1)

which, in turn, accelerates the destruction of the entire cell.

" This is one of the key steps for efficient dismantling of the cell, "

Green said. Not only does the finding help researchers better understand the

fundamental mechanism of how cells die, it also has implications for

advancing knowledge of how the dying cell impacts on the immune system. " We

feel that this event in the dying cell is part of the message which tells

the immune system whether to create an immune response or not, " he said,

explaining this could have implications for some autoimmune diseases, which

result when the immune system mistakenly attacks normal cells.

The discovery is the latest of many important findings from Green, an

eminent scientist who is known the world over for his studies of apoptosis.

" Doug is one of the most cited scientists in biomedical research in the

world, " said Mitch Kronenberg, Ph.D., LIAI President and Scientific

Director, explaining that Dr. Green's scientific findings are consistently

referenced by medical authors and scientists around the globe. " This is a

reflection of the quality and importance of Doug's research. He is one of

the top scientists worldwide studying the process of how cells die. "

Although it sounds contradictory, cell death is key to life. Programmed

cell death is necessary to maintain health as unneeded or unhealthy cells in

the body are killed off to leave room for what is vital. " Cells don't just

die by accident, " explained Green. " They kill themselves. And that's

absolutely essential to our existence as multi-cellular organisms. " Cancer

occurs when cells reproduce out of control and lose the capacity to undergo

programmed cell death, leading to tumors.

" There are many important human diseases where it's thought that the

process of programmed cell death is defective, such as in cancer and some

autoimmune diseases, " said Green. " By better understanding how to trigger

cell death, we may be able to learn how to control it, which could have

major implications for many diseases. "

Kronenberg added that Green's finding is a very important step forward.

" Building on this research, scientists may one day learn to artificially

induce cell death, " he said. " That would allow the body to rid itself of an

unwanted proliferation of cells, such as is found in cancer. "

Other participants in this study include Drs. Jean-Ehrland Ricci,

Cristina Munoz-Pinedo and Fitzgerald of the La Jolla Institute for

Allergy & Immunology, Beatrice Bailly-Maitre of the Burnham Institute and

Guy Perkins, Nagendra Yadava, Immo Scheffler and Mark Ellisman of the

University of California, San Diego.

About LIAI

Founded in 1988, the La Jolla Institute for Allergy and Immunology is a

non-profit medical research center dedicated to increasing knowledge and

improving human health through studies of the immune system. Researchers at

the institute carry out studies designed to understand and lead to the

development of cures for cancer, allergy and asthma, infectious diseases,

and autoimmune diseases such as diabetes, inflammatory bowel disease and

arthritis. The institute's research staff includes over 100 Ph.Ds.

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