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February 22, 2006

Cancer Promoting Protein Shows Up In Unexpected Place In The Cell

Topics: Medicine
Image-right: Two photomicrographs show the movement of the oncogene K-Ras. At the top, K-Ras (blue) is seen at the periphery of the cell; mitochondria are yellow. Below, K-Ras has moved to the mitochondria, which appear rounded and white. Click image to view larger(NYU Med. Ctr.)]

New York University School of Medicine researchers report that they have discovered that a protein widely known to cause the out-of-control growth of cells can actually be manipulated to induce those cells to commit suicide, providing a novel target for the development of anti-cancer drugs.

(...) the researchers report they have discovered a new mechanism that regulates the action of K-Ras, a cellular protein that plays an important role in many human cancers.

(...) Ras proteins have captured the interest of cancer researchers since the late 1970s, when the first oncogenes -- genes that cause the transformation of normal cells into cancerous cells -- were discovered. One of those oncogenes was ras. There are three ras genes, and K-Ras is the most important in terms of its impact on human cancer.

(...) K-Ras acts like as a molecular switch. In its normal form, the protein can be turned on and off to control pathways that regulate cell growth. The mutated form, however, is locked in the "on" position, causing cells to grow uncontrollably and, at the same time, turning off programmed cell death, or apoptosis, the process that tells a cell when it is time to die. The result is cancer.

(...) Until recently, K-Ras was thought to function only at the cell membrane, where the protein is permanently anchored in place by lipid molecules and electrostatic forces. "We discovered that the position of K-Ras in membranes is not permanent, and its positioning can be regulated by a signaling enzyme called protein kinase C," says Dr. Philips.

(...) Unexpectedly, K-Ras began to appear in an unusual place. The current study was then launched to determine what was causing K-Ras to relocate and what it might be doing in its new home.

(...) Dr. Philips and his colleagues discovered that PKC causes a phosphate molecule to be added to K-Ras. This "phosphorylation" process weakens the electrostatic bonds that anchor the protein, allowing it to dislodge from the plasma membrane.

(...) The most intriguing aspect of the study is that it identifies a potential new mode of suppressing tumors, says Dr. Philips. "Our data suggested that if we could find a way to phosphorylate K-Ras, we might be able to promote programmed cell death in tumors driven by the ras oncogene."

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Posted by Richard at February 22, 2006 10:18 PM

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