March 27, 2009

Speaker delves into protein degradation

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Aaron Ciechanover, M.D., D.Sc., at last week’s Discovery Lecture. (photo by Joe Howell)

Speaker delves into protein degradation

What could Charles Darwin and Adolf Hitler possibly have to do with colorectal cancer?

The connection has everything to do with protein degradation, the exodus of Jewish scientists from Nazi Germany and plants that bend to the light, Israeli researcher Aaron Ciechanover, M.D., D.Sc., said during last week's Discovery Lecture.

Jewish scientists helped power new engines of scientific discovery in the United States and in what would become the state of Israel. One of them, a Holocaust survivor named Avram Herschko, M.D., Ph.D., was Ciechanover's thesis adviser at the Technion-Israel Institute of Technology in Haifa.

With their colleague Irwin Rose, Ph.D., at Fox Chase Cancer Center in Philadelphia, Herschko and Ciechanover detailed the ubiquitin proteolytic system of protein degradation. Ubiquitin is the label attached to proteins that are to be degraded by cellular “waste disposers” called proteasomes.

Their discovery, for which they were awarded the 2004 Nobel Prize in Chemistry, has led to what Ciechanover called “four generations” of drug discovery aimed at interrupting diseases of abnormal protein degradation as diverse as cancer, cystic fibrosis and Alzheimer's disease.

The fourth, and current, generation of drug discovery is based on Charles Darwin's theory that “some influence” transmitted from tip to stem enables plants to bend toward the light.
In 1928, a Dutch researcher discovered the source of the influence — a plant hormone later named auxin after the Greek word “to grow.” Auxin works as a kind of “molecular glue,” helping its receptor bind more closely to proteins that are targeted for degradation.

The receptor, it turns out, is also involved in the ubiquitin proteolytic system in higher animals. Since a number of human diseases, including colorectal cancer, are related to an abnormal build-up of proteins, researchers are now searching for small molecules that can provide the human equivalent of auxin — to “glue” proteins that need to be broken down.

In describing Darwin's theory, Ciechanover asked, “What influence?”

“Chemistry,” he answered. “There are no magic influences. It's all about chemistry.”
For a complete schedule of the Discovery Lecture series and archived video of previous lectures, go to