Discovery of cellular 'switch' may provide new means of triggering cell death, treating disease
A research team led by the University of Colorado at Boulder has discovered a previously unknown cellular "switch" that may provide researchers with a new means of triggering programmed cell death, findings with implications for treating cancer.
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The new results are a big step forward in understanding programmed cell death, or apoptosis, a cell suicide process that involves a series of biochemical events leading to changes like cell body shrinkage, mitochondria destruction and chromosome fragmentation, said CU-Boulder Professor Ding Xue. But unlike traumatic cell death from injury, programmed cell death is a naturally occurring aspect of animal development that may help prevent human diseases like cancer and autoimmune disorders, said Xue, lead author on the new study.
In the new study, Xue and his team found that a well-known cellular molecule called caspase - known as the "executioner enzyme" for apoptosis because of its primary role of cutting up and destroying cellular proteins -- has an entirely different effect on a particular enzyme called Dicer. The team found that when caspase cleaves Dicer, it does not kill it but instead changes its function, causing Dicer to break up chromosomes -- pieces of coiled DNA containing thousands of genes -- and kill the cells that house them.
"This finding was totally unexpected," said Xue of CU-Boulder's molecular, cellular and developmental biology department. "We believe that by understanding this mechanism, we may be able to develop a new way to trigger cell death in a controlled manner as a way to treat disease."
A paper on the subject appears in the March 12 issue of Science. Co-authors on the study included CU-Boulder postdoctoral researchers Akihisa Nakagawa and Yong Shi and Tokyo Women's Medical University researchers Eriko Kage-Nakadai and Shohei Mitani.
The normal function of Dicer is to snip strands of RNA into smaller pieces that attach to messenger RNA molecules -- which carry DNA's genetic messages from the nucleus of cells to make specific proteins in cell cytoplasm -- and silence their activity, said Xue. But when caspase comes in contact with Dicer, it takes away Dicer's ability to cleave RNA and it replaces it with the ability to snip up and destroy DNA-laden chromosomes.