A role of glucose tolerance could make the adaptor protein p66Shc a new target for cancer and diabetes

February 13, 2014, Lunenefeld-Tanenbaum Research Institute

A protein that has been known until recently as part of a complex communications network within the cell also plays a direct role in regulating sugar metabolism, according to a new study published on-line in the journal Science Signaling (February 18, 2014).

Cell growth and are tightly controlled processes in our cells. When these functions are disturbed, diseases such as cancer and diabetes occur. Mohamed Soliman, a PhD candidate at the Lunenfeld Tanenbaum Research Institute at Mount Sinai Hospital, found a unique role for the p66Shc adaptor protein in regulating glucose metabolism and . This report could lay the foundation for future studies to target adaptor proteins in cancer and diabetes therapy.

Proteins are functional units of cells that assemble in a precise manner to control cellular processes. Specifically, adapter proteins act as linkers or switches to fine tune cellular functions. Soliman and colleagues became interested in p66Shc adaptor protein after reading that mice deficient in it have a greatly increased lifespan and show no signs of cancer. p66Shc mice also have better glucose tolerance and are resistance to the development of obesity and diabetes. These findings prompted Soliman to take novel approaches to elucidate the mechanism to explain these findings. Briefly, Soliman explains "we found when silencing the adaptor p66Shc in cells, enhances not only , but also the metabolism of and molecules involved in the making the cells building blocks, resulting in overall increased cell growth."

Thus, p66Shc may have evolved to be a switch that responds to nutrient availability. This role of p66Shc as a sensor of energy levels appears to be unique to higher level organisms explains Soliman's mentor Dr. Jim Dennis "the gene responsible for p66Shc protein expression is relatively new by evolution standards, as it is not seen in species other than vertebrates". Simply stated p66Shc acts to suppress insulin signaling and energy metabolism when glucose levels are high, as in the case of diabetes.

Mohamed Soliman is a Vanier scholar and was mentored by the late Dr. Tony Pawson whose research is credited for pioneering the field of signal transduction by first describing in the 1980's that proteins contain modular domains that allow them to interact with each other to control cellular communication. He is currently working in the laboratory of Dr. Jim Dennis, Senior Investigator at the Lunenfeld-Tanenbaum Research Institute, and a professor at the University of Toronto. This study has been done in collaboration with Dr. David Sabatini at the Massachusetts Institute of Technology.

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