Johns Hopkins scientists pull protein's tail to curt...( When researchers look inside human c...)

When researchers look inside human cancer cells for the whereabouts of an important tumor-suppressor, they often catch the protein playing hooky, lolling around in cellular broth instead of muscling its way out to the cells' membranes and foiling cancer growth.

This phenomenon of delinquency puzzled scientists for a long time until a cell biologist in the Johns Hopkins University School of Medicine felt compelled to genetically grab the protein by the tail and then watched as it got back to work at tamping down disease.

"It was curious that when we removed its tail, the protein suddenly was unhindered and moved out to the membrane and became active," says Meghdad Rahdar, a graduate student in pharmacology.

The discovery, published Dec. 15 online at the Proceedings of the National Academy of Sciences, represents a potential new approach to cancer therapy, according to Peter Devreotes, Ph.D., professor and director of cell biology at Johns Hopkins.

"A long-term goal is to find a drug that does the equivalent of our bit of genetic engineering," he says.

The flexible tail contains a cluster of four amino acids the building blocks of proteins that regulate this tumor suppressor known as PTEN. When chemically modified, these amino acids act to "glue" the tail back to the body of PTEN and prevent the attachment of PTEN to the membrane. By genetically removing PTEN's tail, or manipulating the cluster of four amino acids so that they cannot be modified, the researchers persuaded PTEN to move to the cell membrane where it goes about its tumor-suppressing business of degrading a molecular signal called PIP3 that causes errant cell growth.

"As far as I know, I haven't seen anyone activate a tumor suppressor, but we seem to have done it genetically," Rahdar says.

While genetically engineering cancer cells in the human body is neither practical nor safe, manipulating such unbinding of PTEN wit
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