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Death, division or cancer? Newly discovered checkpoint process holds the line in cell division
Date:7/1/2008

for Chemistry along with former Fox Chase researcher Irwin Rose, Ph.D., for the discovery of ubiquitin-mediated protein degradation at Fox Chase.

Their findings show that MCF2 joins a previously known group of proteins the mitotic checkpoint complex to inhibit the pro-division APC/C protein complex. According to Yen, MCC and MCF2 team up to prevent the activation of APC/C by a signaling molecule called Cdc20. "The mitotic checkpoint is a molecular failsafe system, an intricate clockwork mechanism to ensure that everything is working properly before it allows a cell to divide," Yen says.

When sells divide, one of the first steps is to replicate DNA, which are in the familiar X- and Y-shaped structures called chromosomes. Before the cell can split, the mitotic checkpoint proteins monitor the mechanical connection between microtubule fibers (which act like rope to pull apart replicated pairs of chromosomes) and the chromosomes. If everything is in place, the checkpoint proteins release APC/C and allow division to continue. If not, the cell self-destructs before it can divide.

If the checkpoint proteins themselves are faulty, however, mitosis results in aneuploidy, the loss or gain of chromosomes in the daughter cells. This increases the risk of cancer, and promotes the resistance of cancer cells to chemotherapies.

Certain cancer drugs, such as paclitaxel and gemcitabine, exploit the mechanisms of mitosis to kill cancer cells. Although they act through very different mechanisms, both paclitaxel and gemcitabine sabotage the events monitored by the checkpoint proteins, which then leads to cell death. According to Yen, a deeper understanding of the mechanisms of mitosis will make these drugs, and others like them, more effective and more enduring.

While the researchers characterize the discovery as an important step in understanding mitosis, the existence of MCF2 raises more questions than it does answers. "We still ha
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Contact: Greg Lester
gregory.lester@fccc.edu
215-728-2753
Fox Chase Cancer Center
Source:Eurekalert

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