How oxidation regulates cancer-causing gene

March 27th, 2009 - 5:06 pm ICT by ANI  

Washington, Mar 27 (ANI): A researchers duo at the University of Rhode Island has revealed how reactive oxygen species (ROS), a type of stress signal, regulate a cancer causing protein, called Src.

The findings may help understand how this protein normally behaves in human cells, and eventually help in designing drugs to target specific cancers.

Doctoral student David J. Kemble and Professor Gongqin Sun in the URI Department of Cell and Molecular Biology are the first to provide a biochemical mechanism describing how tyrosine kinases sense and respond to oxidation.

It was found that the sensing system was uniquely applicable to two families of proteins implicated in numerous cancers-the Src and Fibroblast Growth Factor Receptor families of tyrosine kinases.

Src was the first enzyme identified as a cancer-causing gene in the early 1900’s.

The researchers said that Src is a master regulator of cell function, controlling cell metabolism, division, and death.

In normal cells, the function of Src is turned off, and it is turned on only when certain stimulatory signals activate it.

In case the regulatory mechanisms that control Src activity are disrupted, Src may be turned on all the time, which turns the host cell into a cancer cell. Thus, it is crucial to understand how Src function is controlled.

It is known that ROSs are produced when the cells are under growth stimulation, and regulate other cellular events.

Evidence has suggested that ROS can directly regulate the function of Src function, and thus indirectly control many cellular processes.

To understand how Src responds to this regulation, the scientists examined all the potential mechanisms, and identified the sensor that enables Src to respond to ROS regulation.

They found that the sensor was also present in several other similar enzymes, mostly in the FGFR family.

“Our results were surprising at first, given that the results contradict some reports in the literature. But there was always a very clear answer to each question we asked. It was both unusual and exciting to see things progress as smoothly as it did,” said Kemble.

Sun said that the mechanism of regulation represented just a small piece of the large puzzle of how Src is controlled in the cells.

“Src function is under the control of several different mechanisms; each one needs to fit in with the others to form a seamless regulatory system.” said Sun.

The results have been published online in the Proceedings of the National Academy of Sciences. (ANI)

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