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UT Southwestern researchers discover master switch in cell death

Researchers at UT Southwestern Medical Center have found an enzyme vital for controlling the early stages of cell death ?a beneficial and normal process when it works right, but malignant in a variety of cancers when it malfunctions.

The researchers are now examining tissue from cancer patients to try to determine how mutations in the enzyme’s gene may relate to cancer.

“We think this gene will really be a hot spot in research,?said Dr. Qing Zhong, postdoctoral researcher in biochemistry at UT Southwestern and lead author of a paper to be published in the July 1 issue of the journal Cell.

The life and death of cells is a complex avalanche of reactions, controlled by a few molecules that sit atop a biochemical “pyramid.?/p>

The newly discovered enzyme, which the researchers have named Mule, destroys a key molecule at the top of the pyramid, thus leading to the cascading disintegration of the cell. Their findings also suggest a new drug target for controlling tumor formation.

Dr. Xiaodong Wang, professor of biochemistry at UT Southwestern and a researcher with the Howard Hughes Medical Institute, said the discovery of Mule will open up a whole field of research to study the enzyme’s role in normal cell death and cancer.

“We think these findings are very significant,?said Dr. Wang, senior author of the Cell study. “This is the first enzymatic step that regulates the degradation of proteins that control cell death.?/p>

The beneficial side of cell death ?known as apoptosis ?occurs when it kills cells at appropriate times, as is the case, for example, when it removes the webbing from the fingers of an embryo or shapes a developing brain. But the darker side of this complex process manifests itself in cancers when cells don’t die when they’re supposed to.

The key to the researchers?finding was the interaction between the Mule enzyme and a major player in cell death, the protein Mcl-1. Dr. Wang said that while there are
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Source:UTSouthWestern


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