Chapel Hill - Scientists at the University of North Carolina at Chapel Hill for the first time have identified the three dimensional crystal structure of two cellular proteins that when bound together play a key role in triggering the spread of cancer cells.

The new findings are published in the December 7 issue of the international science journal Nature. They should help pave the way for deciphering exactly how this protein complex normally functions in the cell's molecular pathway and what can go wrong when either protein is mutated. Given this information, future drug discovery efforts can be aimed at targeting the interaction between specific proteins involved in making cancer cells invasive while causing little or no unwanted side effects.

In their research, scientist headed by John Sondek, PhD, assistant professor of pharmacology at UNC-CH School of Medicine focused on a specific family G proteins important in cellular growth control and architecture.

"You can think of a G protein as a light switch," Sondek said. "And there are many of these proteins in your body that are controlling numerous functions, depending on whether they're switched 'on' or 'off'."

The UNC researcher studies the Rho family of G proteins, which normally help regulate such important functions as cell shape, division, movement, proliferation - virtually every aspect of cellular change and development. In addition, Rho family G proteins are also implicated in malignant growth transformation.

According to Sondek, activation of these G proteins depends on the molecular signal they receive from other proteins called guanine nucleotide exchange factors or GEFs. "If GEFs are in their active form, they in turn activate the G protein. Trouble occurs when you get a perpetual 'on' state for these G-proteins, which can lead to malignancies."

Here, the 'on' position of the light switch occurs when the G protein is bound to the small molecule guanosine triph
'"/>

Contact: Leslie H. Lang
LLANG@MED.UNC.EDU
919-843-9687
University of North Carolina School of Medicine
5-Dec-2000