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Researchers find new piece of cell growth puzzle

pamycin was effective and caused fewer side effects than existing treatments, no one understood exactly how or why it worked.

Using rapamycin as a research tool, Sabatini, then a graduate student at Johns Hopkins Medical School, worked backward--exposing cells to the drug and monitoring its effect. Sabatini discovered that rapamycin blocked the activity of a protein called mTOR (mammalian Target of Rapamycin).

"Rapamycin appears to stop cell growth by flipping a pre-existing switch that cells use to sense nutrients in their environment--the cells are tricked into thinking they're starving," explained Sabatini. Faced with this faux famine, T cells--the cells responsible for organ rejection--stop growing and dividing in the body, staving off rejection.

Further studies suggested that this was just the tip of the iceberg and that rapamycin was inhibiting a larger, nutrient-sensitive pathway helping to control cell growth regulation. This suspicion was confirmed in 2002 when Sabatini's lab identified another protein in the mTOR complex. Raptor (regulatory associated protein of mTOR) was found to work in conjunction with the mTOR protein to directly regulate cell size in response to nutrient levels.

In their newest findings, Sabatini and his colleagues have discovered a third protein, GβL, which stabilizes interactions between raptor and the mTOR protein. The balance between GΒL and raptor might be perturbed in human disease, said Sabatini, and could be a potential target for therapy.

As the puzzle becomes more complete, researchers said, it's clear that the process of cell growth has implications beyond those previously thought. "In some cases, a cell becomes insensitive to nutrient signaling and growth goes out of control. This suggests that the appreciation of the role of nutrients and signaling has been underestimated in the study of cancer," noted Sabatini.

This seems to be the case in tumors caused by tub
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Contact: Kelli Whitlock or Melissa Withers
newsroom@wi.mit.edu
617-258-5183
Whitehead Institute for Biomedical Research
30-Apr-2003


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