Chuck Bednar for redOrbit.com – @BednarChuck
A newly-discovered process used by the dividing cells in worms to make sure that the processes of gene expression is properly coupled to cell division to ensure that the organism can develop as expected – a finding that could also have implications for cancer research in humans.
Writing in the journal Current Biology, biologists from the University of Iowa explain that the same mechanism that they observed in the worm may be taking place in people, ensuring proper development. It involves a part of the cell known as the centrosome, which functions like a sort of “internal timekeeper,” and a crucial protein that is in charge of gene expression.
How the centrosome oversees beta-catenin distribution
UI integrated biology doctoral candidate and first author Setu Vora and his colleagues compare the centrosome to a train conductor and the protein, beta-catenin, to a hitchhiker that boards the cellular train and ensures that cells grow like they should. In this process, timing is everything, as the right processes need to take place at the right time for a person to be healthy.
Beta-catenin attaches itself to the centrosome to ensure that it can be properly regulated as well as divided out to newly-forming cells in just the right amounts. Since most tumors tend to have severe centrosome abnormalities, Vora explained, similar mechanisms involving the centosome could also be relevant in cancer and other human illnesses.
The centosome acts like the captain of the cell division process, the UI researchers said, and is responsible for ensuring that new cells are given equal portions of DNA when they are originally created. The new research reveals that it serves as the timekeeper of cell division processes, such as those involving beta-catenin, the protein responsible for controlling gene expression.
“The inspiration for this research is, in a nutshell, understanding how gene expression works specifically through the regulation of an important protein called beta-catenin,” Dr. Bryan Phillips, assistant professor of biology at the university and corresponding author of the study, explained to redOrbit via email. “Beta-catenin controls gene expression in all animals and has important roles instructing cells during human development and even in adults.”
“We study beta-catenin regulation in a experimentally amenable genetic model system, the nematode C. elegans,” he added. “We find that beta-catenin levels build up on a cellular structure called the centrosome just before a cell divides. Because of this localization pattern, beta-catenin is degraded. As the centrosome grows and matures during the cell cycle, it accumulates and destroys more and more beta-catenin. This novel mechanism means beta-catenin levels are kept low in both daughter cells after division.”
The importance of limiting beta-catenin amounts
Beta-catenin is present in cell division, but begins to degrade during the process, limiting the amount of itself is passed on to its daughter cells. The amount of beta-catenin given to each one is dependent upon the type of cell that it is. The UI team found that the protein only knows how much of itself to distribute to forming cell because it attaches to the centrosome.
Those timekeepers grow and mature inside of cells just as those cells begin dividing, and while it might seem unorthodox for an essential part of a cell to activate just before it starts dividing, the study authors explain that this allows a mature centrosome to act like an internal alarm alerting the body when a cell is about to divide. At that very moment, the beta-catenin becomes attached to the centosome, and they begin to work together to ensure the process goes smoothly.
Typically, the two newly forming daughter cells only inherit a little beta-catenin, but when Vora and his colleagues blocked the protein’s ability to hitchhike on the centrosome, those daughter cells ended up receiving too much of the substance, which caused some of those cells to wind up converting into completely different types of tissue.
“When beta-catenin levels are too high, birth defects or cancer can occur. For instance over 90 percent of colorectal cancers have high, unregulated levels of beta-catenin. So there is a great deal of interest in answering the following questions: How beta-catenin is regulated? How are its levels kept in check?” Dr. Phillips told redOrbit via email.
“The implications for cancer is that this centrosomal localization pattern is also seen in mammals,” he added. “Our finding therefore suggest that the centrosomal regulation mechanism might also be well-conserved. Further, cancer cells often exhibit aberrant centrosomes (both the number and shape of the centrosomes are unusual). Could the centrosome-associated mechanism that regulates beta-catenin levels also be aberrant in these tumor cells? Only further study will tell us.”
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