Monday, May 5, 2003

Cleveland Clinic-Led Research Identifies Two Proteins Required For Completion Of Cell Division

Results Identify Promising Novel Targets For Anti-Tumor Drugs

Research at The Cleveland Clinic has resulted in the identification of two proteins required in cell division, a find with potentially significant implications for the development of highly targeted anti-tumor drugs.

The proteins, Syntaxin 2 and Endobrevin, were identified by a team of scientists led by Thomas Weimbs, Ph.D., a researcher in The Cleveland Clinic Department of Cell Biology. Prior to this study, researchers knew that Syntaxin 2 and Endobrevin were involved in the fusion of cell membranes. Through their lab work, however, Dr. Weimbs and his colleagues determined that Syntaxin 2 and Endobrevin also play a key role in cytokinesis, or cell division.

“This is very significant because cytokinesis is a fundamental process common to all organisms,” Dr. Weimbs said. “Understanding the role of Syntaxin 2 and Endobrevin in cytokinesis is especially important because cancer cells use the same cell-division mechanism to proliferate. Our hope is that identifying the involvement of these proteins in the final stages of cytokinesis will allow for the development of much more specific anti-tumor drugs.”

Cytokinesis involves the ingression of the membrane in the middle of cells to separate, much like a sausage would require the tightening of a string around it to divide into links. Ingression of the cell membrane leads to two prospective daughter cells connected by a tiny bridge called a midbody. The cell finally divides after the midbody splits in a process called abscission, the least understood step in cell division.

The work of Dr. Weimbs and his colleagues showed for the first time that midbody abscission requires the function of Syntaxin 2 and Endobrevin, proteins that belong to a protein family called “SNAREs.” The researchers found that when they inhibited the function of either protein, cells became stuck in the midbody stage and after two hours gave up their midbody structure to form cells with two nuclei.

The researchers’ findings appear in the May 6 issue of Developmental Cell, a leading molecular and cell biology journal affiliated with Cell magazine. Seng Hui Low, Ph.D., a senior scientist in Dr. Weimbs’ laboratory was the primary researcher of this study, which also includes Beatriz Quinones, Ph.D., a researcher at the University of California at Berkeley.

Dr. Weimbs and his colleagues currently are investigating how Syntaxin 2 and Endobrevin are transported to the midbody during cell division and how their function is regulated. Understanding this process may allow the researchers to find ways of inhibiting cell division with drugs.

The Cleveland Clinic Foundation, founded in 1921, integrates clinical and hospital care with research and education in a private, not-for-profit group practice. Approximately 1,100 full-time salaried physicians at The Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2001, there were more than 2.25 million outpatient visits to The Cleveland Clinic Foundation. Patients came for treatment from every state and from more than 80 countries. There were nearly 52,000 hospital admissions to The Cleveland Clinic in 2001. The Cleveland Clinic website address is www.clevelandclinic.org.

Contacts:

Jim Armstrong, 216/444-9455

Cole Hatcher, 216-445-1991

Russell J. Vanderboom, Ph.D., 216/444-5830