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New Discovery May Lead To Control Of Production Of Key Proteins

WINSTON-SALEM, N.C. -- Scientists are closing in on discovering the way that the body regulates critical proteins involved in the front line defense against disease as well as in normal body processes.

The discoveries could lead to development of pharmaceuticals to control the body's production of these proteins.

An article in the April 16 issue of Science, for the first time links the destruction of proteins to the destruction of the molecules that create those proteins, called messenger RNA. Gary Brewer, Ph.D., associate professor of microbiology and immunology at Wake Forest University Baptist Medical Center, is a co-author,

Brewer said the messenger RNAs under study encode many proteins of high interest in medicine: cytokines, which are important for immune response -- the defense against disease-- and cell development; oncoproteins, important for both normal cell growth and in the uncontrolled cell growth of cancer; and proteins that directly affect heart function.

The new results build upon previous discoveries by Brewer and his colleagues, dating back to 1986. One key discovery, in 1991, was of a protein that they called AUF1, which binds to the messenger RNA.

"It has been known for some number of years that there are enzymes that are involved in the degradation process of proteins, just as there are enzymes that are involved in the degradation process for messenger RNA," Brewer said.

One enzyme involved in the destruction of proteins is called the proteasome. "One of the implications of this work in terms of mechanism is that this protein, AUF1, binds to the RNA targeting sequences, which makes the messenger RNA unstable," Brewer said.

"How does the degradation of messenger RNA occur? What this paper would seem to indicate is that the proteasome's destruction of AUF1 somehow permits the degradation of the messenger RNA to which AUF1 is binding."

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Contact: Robert Conn, Mark Wright or Jim Steele
rconn@wfubmc.edu
336-716-4587
Wake Forest University Baptist Medical Center
16-Apr-1999


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