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Molecular switch identified that controls key cellular process
Date:8/1/2012

New York, NY and Oxford, UK, August 1, 2012 The body has a built-in system known as autophagy, or 'self-eating,' that controls how cells live or die. Deregulation of autophagy is linked to the development of human diseases, including neural degeneration and cancer.

In a study published online this week in the Proceedings of the National Academy of Sciences, scientists at the Ludwig Institute for Cancer Research in Oxford discovered a critical molecular switch that regulates autophagy. They also studied the links between autophagy and a cellular process called senescence that stops cell growth permanently.

The researchers identified ASPP2, a tumor suppressor, as a molecular switch that can dictate the ability of a common cancer gene, known as the RAS oncogene, to either stop or promote senescence.

As Yihua Wang and researchers in Xin Lu's group at the Ludwig Institute investigated the life cycle of fibroblast cells the most common connective tissue cells in animals they found that reduced levels of the ASPP2 protein increase RAS oncogene-induced autophagic activity. This in turn prevented cells from entering senescence. Without ASPP2, the cells continued to proliferate unchecked, thereby promoting tumor growth.

ASPP2 is known to play a role in suppressing tumor development. Mice that have a deficiency or malfunction in this protein have a predisposition to developing tumors. And low ASPP2 levels in patients are linked to poor prognoses in cancers, such as large B-cell lymphomas. Reduced ASPP2 expression has also been observed in highly metastatic breast tumors. But until now, researchers did not understand why.

"We found that in the presence of the common cancer-causing RAS oncogene, ASPP2 interacted with a protein complex that is responsible for deciding cell fate via autophagy," said Yihua Wang, PhD, Ludwig researcher in Oxford.

"What this means is that the cell's emergency stop button is d
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Contact: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Source:Eurekalert

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