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St. Jude finds mechanism for faulty protein disposal
Date:12/6/2007

A discovery by St. Jude Childrens 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 this mechanism. 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 lymphocytesimmune 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 papers senior author. Our study sheds new light on how that process works.

The St. Jude team focused their investigation on special channels called retrotranslocons in the membrane of the cells protein factory. The researchers also studied a small collection of molecules that pull defective proteins out of the factory through the retrotranslocon so they can be delivered to the cells protein shreddera structure called the proteasome.

The protein factory, called the endoplasmic reticulum, is somewhat like an origami workshop: In the endoplasmic reticul
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Contact: Summer Freeman
summer.freeman@stjude.org
901-495-3061
St. Jude Children's Research Hospital
Source:Eurekalert

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