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St. Jude Finds Mechanism for Faulty Protein Disposal
Date:12/6/2007

Discovery shows how a group of molecules pulls certain types of defective proteins out of the cell's protein factory, a finding that could help development of new cancer drugs

MEMPHIS, Tenn., Dec. 6 /PRNewswire-USNewswire/ -- A discovery by St. Jude Children's Research Hospital scientists offers new insights into how myeloma cells dispose of defective or excess proteins and could lead to new cancer treatments.

The researchers identified key cellular components that carry out protein disposal, a finding that helps to explain how cancer drugs called proteasome inhibitors interfere with this process. The discovery is important because the newly identified components of the protein disposal mechanism could be targets for novel cancer drugs designed to kill the cell by blocking disposal of defective proteins. A report on this work appears in the Nov. 30 issue of "Molecular Cell."

Myelomas are cancers of plasma cells, which are the "activated" form of B lymphocytes--immune system cells that respond to infection by temporarily producing extremely large amounts of proteins called antibodies that attack the target. The rapidly multiplying cancer cells continually make large numbers of new antibodies, which increases the chance for errors in the production process, resulting in the accumulation of defective proteins that must be degraded.

"Proteasome inhibitors are currently being used to treat some types of cancer including multiple myelomas, although many aspects of this cellular process remain poorly understood," said Linda Hendershot, Ph.D., a member of the St. Jude Department of Genetics and Tumor Cell Biology, and the paper's senior author.

"The results of our study help to explain how the process works and how we might design ways to block it in myelomas," said Yuki Okuda-Shimizu, Ph.D. a postdoctoral fellow in Hendershot's laboratory who contributed significantly to the project.

This work was supported by
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SOURCE St. Jude Children's Research Hospital
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