Scientists identify role of important cancer protein

UPTON, NY -- Scientists working at the National Synchrotron Light Source (NSLS) at the U.S. Department of Energy's (DOE's) Brookhaven National Laboratory have unveiled the details of an important cancer protein. Though the protein, called Ski (for Sloan Kettering Institute, where it was identified in the early 1980s), is known to trigger tumor growth, how it does this is still not well understood. The new results, which are reported in the November 1 issue of Cell, shed light on this process and may provide ways to design new anticancer drugs.

"We now have a very important clue as to how Ski interferes with key proteins that prevent cells from becoming cancerous," says Yigong Shi, a molecular biologist at Princeton University and leader of one of the two teams that conducted the study. "Understanding how to stop Ski from disrupting the normal function of cells will probably be key to developing new anticancer drugs."

Ski prevents a protein called transforming growth factor-beta (TGF-b) from safeguarding cells against excessive growth. "TGF-b acts like a molecular traffic light, ordering certain cells to slow down and stop dividing," Shi says. "When TGF-b is blocked, for example by Ski, cells manage to speed through this checkpoint, triggering runaway cellular growth that eventually results in cancerous tumors."

TGF-b cannot enter cells, so it transmits its signal inside the cell by attaching to receptor proteins on the cell's outer surface. The signal generated by this interaction is carried across the cell membrane to proteins inside the cell. Some of these signaling proteins are triggered inside the cell cytoplasm and later bind to other proteins inside the nucleus. The combination of both types of signaling proteins activates genes necessary for the normal functioning of the cell.

Ski, which is already present in the human body, disrupts the signaling proteins when it is either overexpressed or introduced by a virus inside the bo

Contact: Karen McNulty Walsh
DOE/Brookhaven National Laboratory

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