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Gene linked to enlargement of the factory where proteins are processed

Part of a cellular mechanism that regulates the folding of new proteins into their proper shapes also includes a genetic response that enlarges the factory where both protein folding and packaging of proteins occurs. This finding, from researchers at St. Jude Children's Research Hospital, Loyola University (Chicago) and Kyoto University (Kyoto, Japan), are published in the Oct. 15 issue of the Journal of Cell Biology.

The link between protein folding and factory construction ensures that the two processes are coordinated when the cell is called upon to quickly make, fold and secrete large amounts of specific proteins.

The investigators discovered that the cell makes a molecule called XBP1 in response to an increased demand on the protein-folding machinery. This increased demand for folded proteins triggers the so-called unfolded protein response (UPR), as well as the expansion of the factory where proteins are folded and packaged so they can be secreted from the cell. The UPR also prompts the cell to make molecules called chaperones, which do the actual task of protein folding.

XBP1 triggers the cell to make phosphatidylcholine, the major building block of the rows of membranes that make up much of the factory, which is called the endoplasmic reticulum (ER). Membranes in the ER serve as envelopes to package the folded proteins.

After leaving the ER, the envelope fuses with the inside face of the membrane that surrounds the cell itself. Once fused to the cell's membrane, the envelope pops open, ejecting the protein out of the cell.

"By linking chaperone production to the synthesis of phosphatidylcholine, XBP1 coordinates the processes of building and equipping new ER to increase the cell's capacity for folding and shipping proteins," said Suzanne Jackowski, Ph.D., a member of St. Jude Infectious Diseases. Jackowski is an author of the Journal of Cell Biology report.

The study explains how the cells are able to rapidly meet the need fo
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
1-Nov-2004


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