Scientists pull protein's tail to curtail cancer

Dec 31, 2008

(PhysOrg.com) -- 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 with drugs is a viable alternative to guard against cell overgrowth, the hallmark of cancer, the Hopkins scientists say.

In many tumors, PTEN is simply not present. In others, it's there, but a key enzyme that produces PIP3 is over-activated. The Hopkins team already has shown the first evidence that adding the modified PTEN to cells that lack PTEN not only restores normal enzyme levels but ramps up PTEN activity and quells the cell growth signal.

On the Web:

www.hopkinsmedicine.org/cellbio/devreotes
www.pnas.org

Provided by Johns Hopkins Medical Institutions

Explore further: Team finds new genetic anomalies in lung cancer

add to favorites email to friend print save as pdf

Related Stories

Cell growth discovery has implications for targeting cancer

Oct 11, 2013

The way cells divide to form new cells—to support growth, to repair damaged tissues, or simply to maintain our healthy adult functioning—is controlled in previously unsuspected ways UC San Francisco researchers have discovered. ...

Molecule necessary for DNA repairs also halts them

May 07, 2012

(Phys.org) -- Repairing DNA breaks can save a cell’s life—but shutting off the repair machinery can be just as critical. How cells accomplish this feat was unknown. However, new research by Johns Hopkins scientists, ...

Recommended for you

Bone loss drugs may help prevent endometrial cancer

5 hours ago

A new analysis suggests that women who use bisphosphonates—medications commonly used to treat osteoporosis and other bone conditions—have about half the risk of developing endometrial cancer as women who do not use the ...

Putting the brakes on cancer

Dec 19, 2014

A study led by the University of Dundee, in collaboration with researchers at our University, has uncovered an important role played by a tumour suppressor gene, helping scientists to better understand how ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.