Control sought of cell ‘janitors’ to fight diseases

? The cells in your body are cluttered with trash — unneeded or abnormal stuff that can make you sick or even kill you. Fortunately, nature has provided each cell with its own garbage-disposal system to get rid of dangerous junk.

A crew of 76 chemical agents acts like tiny janitors, prowling the innards of a cell and tagging waste materials so other minuscule cleanup workers can find and destroy them.

Researchers at many laboratories are discovering new details about this ingenious process, in hopes that their findings will lead to new treatments for cancer, Alzheimer’s, Parkinson’s and other diseases.

“In the last three years there has been an enormous amount of work to try to understand how this system works,” said Cecile Pickart, a molecular biologist at Johns Hopkins University in Baltimore. “It’s very exciting when you find new ways of going at disease.”

This waste-disposal apparatus is known as the ubiquitin system because it’s ubiquitous, meaning everywhere.

Ubiquitin is a small protein, consisting of 76 amino acids — chemical compounds made mostly of carbon, hydrogen, nitrogen and oxygen.

Proteins, the building blocks of all living organisms, may contain hundreds or thousands of amino acids, linked together in long chains and folded in various complicated ways, like a tangled ball of yarn. A protein is destroyed — scientists say “degraded” — by unwinding the ball, breaking up the chain and freeing its amino acids to be recycled.

A cell subjected to starvation, radiation, poisoning or infection often contains damaged proteins that must be eliminated. Failure of the ubiquitin system to remove such materials can allow uncontrolled cell growth, the first step toward cancer.

Understanding exactly what goes wrong in the ubiquitin-proteasome machinery could help explain why some cells turn cancerous, long before they are detected by conventional methods.

Already, drugs that control the proteasome are in clinical trials for the treatment of multiple myeloma, an incurable cancer of the bone marrow, Pickart said. In preliminary tests of one such drug, 70 percent of a group of patients with advanced myeloma saw their conditions stabilize or improve, according to researchers at the Dana-Farber Cancer Institute in Cambridge, Mass.