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UCLA researchers uncover new cell biological mechanism that regulates protein stability in cells
Date:12/23/2010

The cell signaling pathway known as Wnt, commonly activated in cancers, causes internal membranes within a healthy cell to imprison an enzyme that is vital in degrading proteins, preventing the enzyme from doing its job and affecting the stability of many proteins within the cell, researchers at UCLA's Jonsson Comprehensive Cancer Center have found.

The finding is important because sequestering the enzyme, Glycogen Synthase Kinase 3 (GSK3), results in the stabilization of proteins in the cell, at least one of which is known to be a key player in cancer, said Dr. Edward De Robertis, senior author of the study and a Jonsson Cancer Center scientist.

"Surprisingly, we found that the degradation of about 20 percent of proteins in the cell is triggered by the GSK3 enzyme," said De Robertis, who also is a Howard Hughes Medical Institute investigator. "That's a great many proteins and one of them, beta-Catenin, is known to cause cancer. We also know that Wnt signaling is activated in about 85 percent of colorectal cancers and other forms of cancer start with mutations that activate Wnt signaling. So, this finding could have ramifications for potential new treatments for cancer."

The study, a collaboration with cell biologist Dr. David D. Sabatini of New York University, appears in the Dec. 23, 2010 issue of the peer-reviewed journal Cell.

De Robertis said Wnt signaling requires inhibition of GSK3, but the enzyme sequestration mechanism was not known until now. The enzyme becomes imprisoned inside membrane-bounded organelles, known as multivesicular bodies, found within the cell cytoplasm.

"We knew these multivesicular bodies were involved in degradation of proteins, but that they had a role in how cells communicate with each other by switching on a signaling pathway was not known," De Robertis said. "This finding raises the possibility that other signaling pathways could operate through this sequestration mechan
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Contact: Kim Irwin
kirwin@mednet.ucla.edu
310-206-2805
University of California - Los Angeles
Source:Eurekalert  

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UCLA researchers uncover new cell biological mechanism that regulates protein stability in cells
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