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MSKCC researchers uncover structure of key protein complex in cells

Scientists at Memorial Sloan-Kettering Cancer Center (MSKCC) have uncovered the structure of a network of proteins that help regulate the life cycle of cells. Understanding the network's physical layout is an important step toward learning its precise function, and in finding ways to correct flaws in the system that could lead to cancer.

Using x-ray crystallography, the researchers identified how one protein, a molecule called the Small Ubiquitin-related Modifier (SUMO-1), is connected or "conjugated" to another molecule within the complex. The findings, reported in the June 2, 2005, issue of Nature, offer the first complete look at the structure of these molecules as they are thought to exist in the cell.

"Understanding this process could be important in many physiological steps that are disrupted in cancer -- including error-prone DNA replication, chromosome segregation, the cell's response to stress, and normal signaling reactions," said Christopher Lima, PhD, a structural biologist at the Sloan-Kettering Institute and lead author of the study.

While there's no direct evidence that SUMO is important in cancer, research suggests that it is necessary for the normal assortment of chromosomes immediately before a cell splits. Yeast cells that lack SUMO cannot successfully divide, Dr. Lima noted.

Since cancer is characterized by cells dividing unchecked, proving SUMO's function could potentially yield novel anticancer therapies. "If sumoylation (when SUMO attaches to a protein) is promoting cell division, then inhibitors of SUMO may be a pretty good agent to block the cell cycle," said Dr. Lima.

Postdoctoral researcher David Reverter, PhD, collaborated with Dr. Lima on the work and is the first author on the Nature paper.

SUMO has been called a "mysterious cousin" of ubiquitin, a protein of increasing interest to cancer experts. The two molecules have remarkably similar structures, though they perform different tasks in c
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Source:Memorial Sloan-Kettering Cancer Center


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