By helping to explain how cells make life and death decisions, a new study by University of Guelph researchers might ultimately help improve drugs and therapies for treating ailments from cancer to Alzheimer’s and Parkinson’s disease.
The most recent study by Prof. Richard Mosser, Molecular and Cellular Biology, appears online this month in the Journal of Biological Chemistry. He also co-authored a related paper last year in the journal Cell Death and Disease.
In both studies, his team, including graduate student and lead author Rabih Roufayel, looked at how a heat shock protein (HSP70) made by cells under stress prevents normal cell death. Called apoptosis, that process occurs all the time as new cells replace old ones.
Certain diseases occur when too many cells succumb, as in neurological ailments such as Alzheimer’s disease or Parkinson’s disease. But other diseases, notably cancer, occur when cells refuse to die.
“Tumour cells often have elevated levels of heat shock proteins including HSP70,” Mosser said, which can help those cells survive.
His team’s new paper shows how a protein called CDK5 regulates production of a small RNA molecule called miR-23a. In turn, that microRNA molecule affects another protein called NOXA that promotes cell death.
The Guelph researchers showed how the “death promoter” works in their earlier paper.
They found that cells under higher temperature have less of this microRNA. That allows cells to make lots of the death-promoting protein, resulting in apoptosis.
But they found that cells expressing HSP70 have more miR-23a; those cells stave off death. Their new paper shows that HSP70 also allows CDK5 to work normally in stressed cells.
High amounts of both CDK5 and miR-23a are associated with cancer development, says Mosser. Drug companies are looking at CDK5 inhibitors for potential cancer therapies.
“By identifying miR-23a as a target of CDK5 and finding that miR-23a determines whether a death-inducing protein is made, our research suggests that drug companies might also consider strategies to inhibit this microRNA to make chemotherapeutic drugs more effective,” said Mosser.
He studies how cells tolerate stress, especially stress treatments that cause protein damage leading to cell death.