Scientists Detail Parts Of Biological "Motor" Key To Cell Life
- Date:
- February 22, 2001
- Source:
- Ohio University
- Summary:
- Scientists studying cellular division have longed for clues to how cancer cells are able to divide so rapidly. Now, studies by Ohio University biochemists are offering several new pieces needed to solve that mystery.
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BOSTON – Scientists studying cellular division have longed for clues to how cancer cells are able to divide so rapidly. Now, studies by Ohio University biochemists are offering several new pieces needed to solve that mystery.
In work presented Feb. 20 at the Biophysical Society annual meeting in Boston, scientists detail how key parts of a biological "motor" essential to the health of cells in all living creatures work together to transport materials during cell division and in other cellular processes. Understanding the design of this motor could help researchers stop its activity when cell division goes haywire, as it does with cancer.
Every cell contains an assembly of proteins that acts like a motor on a one-way train: it quickly and efficiently moves materials such as chromosomes from the edge of the cell to the center. This protein motor, called dynein, is believed to be made up of 12 specialized parts, said Elisar Barbar of Ohio University.
"It is fundamental to the life of the cell. If you remove one piece of the protein the cell will die," said Barbar, an assistant professor of chemistry and biochemistry in the College of Arts and Sciences and lead researcher on the study, part of which also appears this month in the journal Biochemistry.
Barbar and her colleagues have focused their studies on several of the 12 pieces of dynein, including one known as LC8. Studies of fruit flies suggest that mutations of LC8 can cause sterility, neural defects and even death.
Much like a jigsaw puzzle, each part of the dynein protein must have a specific shape or structure and be in a certain position to lock together, which is crucial to the function of the motor, Barbar said. Her research team has located specific spots where some of the pieces are linked together, and also is examining where the parts of the protein latch onto its cargo – chromosomes and other materials – to move it across the cell.
Once scientists understand how the parts of dynein work, they hope to learn whether they can disable the protein during the abnormal cell growth of cancer. If researchers can stop dynein from transporting chromosomes, the cells won't divide, explained Michael Hare, an Ohio University research assistant professor who collaborated on the research, which is supported by a $150,000 grant from the National Institutes of Health.
Such a finding would make possible the development of drugs to attack the protein's function. It's a strategy similar to the one used with the anti-cancer drug Taxol, which destroys the pathways on which the dynein travels. "You can either pull up the train tracks or destroy the engine – it will have the same effect," Hare said.
But scientists first must learn more about how the parts of dynein function, Barbar said. Research on dynein is in its infancy, as technologies such as mass spectrometry and nuclear magnetic resonance (NMR) have only recently been used by scientists to examine the protein's structure at the atomic level.
Though the research was conducted on proteins derived from the fruit fly, the findings have implications for humans as well, Barbar noted. "LC8 is virtually the same in humans as it is in flies, so it must be so important that it didn't change through evolution," she said.
Co-authors on the Biochemistry paper were Brian Kleinman and Daniel Imhoff, undergraduate students at Ohio University, and Thomas S. Hays and Mingang Li of the University of Minnesota. The research also is funded by the Ohio Cancer Research Associates and the American Cancer Society.
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