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Rictor protein offers scientists a new molecular target for cancer therapies
Date:10/28/2010

BOSTON The discovery that a protein called Rictor plays a key role in destroying a close cousin of the AKT oncogene could provide scientists with a new molecular target for treating certain cancers, including breast cancer. Described in the September 2010 issue of the journal Molecular Cell, the study was led by scientists at Beth Israel Deaconess Medical Center (BIDMC).

The oncogenic cousin, known as SGK1, resembles the widely known AKT oncogene in structure, according to the study's senior author Wenyi Wei, PhD, of the Department of Pathology at BIDMC and Assistant Professor of Pathology at Harvard Medical School (HMS).

"If we put the two proteins together, they are very similar," explains Wei. "But in one important way they are very different. AKT is stable, it lives for a long time. But SGK1 has a very short lifespan, and proteins with short lifespans tend to be powerful. Everybody's eye [has been] on AKT, but you have to wonder if this little cousin of AKT can do all the things AKT does." Wei and his team, therefore, set out to better understand how cells control SGK1.

Previous research showed that the protein Rictor forms a multi-protein complex called mTORC2 that activates both AKT and SGK1. Wei's team cultured cells lacking Rictor to observe the effect on SGK1. Surprisingly, they found that SGK1 levels increased.

"We said, that cannot be," notes Wei. "How could we get rid of the protein kinase that activates SGK1 and still have the SGK1 levels be heightened?"

They found their answer when they observed that the cells weren't producing more SGK1; rather, SGK1 was living longer. This suggested to the scientists that Rictor might be playing a role in the destruction of SGK1. And, in subsequent experiments, Wei found that SGK1 is indeed held in check by a protein complex made up of Rictor, Cullin-1, Rbx1, and possibly other components. The protein complex forms a cellular garbage collector called a
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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