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UCSF biochemist wins prestigious prize
Date:12/23/2011

olled, however, to ensure that the body does not poison itself by releasing toxic proteins that are not processed correctly. The unfolded protein response is one of the main ways cells maintain this control.

Basically, explained Walter, "The unfolded protein response makes life and death decisions for the cell."

Those decisions happen in an involuted compartment found within cells known as the endoplasmic reticulum (ER), which can be thought of as a cell's warehouse and way station rolled into one. The vast majority of all the proteins a cell produces are assembled, processed, and packaged there, and the ER ensures that proteins are folded correctly into their final shape and that no misfolded, and potentially malfunctioning and toxic, proteins are released into surrounding tissues.

The ER warehouse can become overworked and too crowded at times, putting stress on cells. When stressed, cells can exercise a sort of nuclear option, switching on a program known as apoptosis and killing themselves. The unfolded protein response is a fail-safe switch in this mechanism. It can pull a cell back from the edge by making more ER, expanding capacity for more proteins to fold properly, thereby relieving the stress.

A few years ago Walter discovered the lynchpin in the process, a protein known as IRE1. This protein is a molecular detector in the ER that gauges when things become too crowded and triggers cell changesthat expand ER space.

This process can also go awry, and when it does, it can lead to a number of different diseases, including cancer. In multiple myeloma, for instance, IRE1 appears to go haywire and the cancer cells "forget how to die," as Walter described it.

Blocking the IRE1 protein with small molecules may help people with this form of cancer, he saida therapeutic possibility that Walter and his colleagues are actively pursuing.

"The Paul Ehrlich and Ludwig Darmstaedter Prize is particularly specia
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Contact: Jason Socrates Bardi
jason.bardi@ucsf.edu
415-502-6397
University of California - San Francisco
Source:Eurekalert  

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