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

Each day, a staggering number of cells perform a feat that still amazes researchers with its complexity: they divide to produce perfect replicas of each other. The process is called mitosis, and an inability to control it is one of the hallmarks of cancer.

Little is known about the biochemical processes that control mitosis, but now researchers from Fox Chase Cancer Center and Technion-Israel Institute of Technology in Haifa, Israel, have discovered a novel activity, called the mitotic checkpoint factor 2 (MCF2). This appears to be integral in preventing cells that are unable to equally separate their chromosomes from dividing. The identities of the proteins involved in MCF2 remain to be determined, however, their findings offer insight into a fundamental question of biology, which may also help to increase the efficiency of cancer drugs that disrupt DNA replication, like gemcitabine, or drugs that prevent mitosis, like paclitaxel.

They publish their findings today online in the Early Edition of the Proceedings of the National Academy of Sciences.

"At any given moment, 250 million cells in your body are undergoing mitosis in order to replenish cells that die as a result of normal turnover," says Tim J. Yen, Ph.D., senior member at Fox Chase. "The mitotic checkpoint is a complex series of quality control systems, just like in a factory assembly line, that ensures that each new cell gets their proper share of DNA."

"Cancer cells tend to bypass quality control, such as the mitotic checkpoint, so as to allow them to shuffle their deck of chromosomes to select for traits that promote drug resistance and the ability to divide uncontrollably," says Yen.

Yen, along with visiting researcher Avram Hershko, Ph.D., of Technion, discovered the ability of MCF2 to block mitosis by shutting down an ubiquitin ligase enzyme known as the anaphase-promoting complex/cyclosome (APC/C). Hershko was awarded the 2004 Nobel Prize 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 have a lot to understand in how all the components of the mitotic checkpoint fit together and even more to understand in how the chromosomes are aligned and separated so exactingly," Yen says.


'/>"/>

Contact: Greg Lester
gregory.lester@fccc.edu
215-728-2753
Fox Chase Cancer Center
Source:Eurekalert

Related biology news :

1. A unique arrangement for egg cell division
2. A study reveals how cells communicate to activate the cell division machinery
3. Newly created cancer stem cells could aid breast cancer research
4. Newly-identified exercise gene could help with depression
5. Newly defined signaling pathway could mean better biofuel sources
6. Newly identified role for power plants in human cells could lead to targeted therapies
7. New, more direct pathways from outside the cell-to-cell nuclei discovered
8. New continent and species discovered in Atlantic study
9. Ancient organisms discovered in Canadian gold mine
10. New golden frog discovered in remote region of Colombia
11. Antioxidant to retard wrinkles discovered by Hebrew University researcher
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/18/2017)... -- Socionext Inc., a global expert in SoC-based imaging and computing solutions, ... which features the company,s hybrid codec technology. A demonstration utilizing TeraFaces ... will be showcased during the upcoming Medtec Japan at Tokyo Big ... Las Vegas Convention Center April 24-27. ... Click here for an image of ...
(Date:4/13/2017)... SANTA MONICA, Calif. , April 13, 2017 /PRNewswire/ ... New York will feature emerging and ... Innovation Summits. Both Innovation Summits will run alongside the ... variety of speaker sessions, panels and demonstrations focused on ... east coast,s largest advanced design and manufacturing event will ...
(Date:4/11/2017)... 11, 2017 Crossmatch®, a globally-recognized leader ... today announced that it has been awarded a ... Activity (IARPA) to develop next-generation Presentation Attack Detection ... "Innovation has been a driving force within Crossmatch ... allow us to innovate and develop new technologies ...
Breaking Biology News(10 mins):
(Date:4/20/2017)... Diego, CA (PRWEB) , ... April 20, 2017 , ... ... management of clinical trials worldwide, announced today that they were named one of the ... , which covers the latest developments in the pharmaceutical industry. , “We take pride ...
(Date:4/19/2017)... ... 18, 2017 , ... The Vibrating Orifice Aerosol Generator (VOAG) ... monodisperse droplets of known diameters for research applications such as for calibrating droplet ... drying monodisperse droplets. , The VOAG requires forcing liquid out of an ...
(Date:4/19/2017)... ... April 19, 2017 , ... ThermaGenix, the PCR Improvement Company, ... to several other early achievements at ThermaGenix, including the business formation and licensing ... ThermaGenix will use proceeds from the Series A-1 round to:, ...
(Date:4/19/2017)... and WESTMINSTER, Colo. , April ... an industry-leading specialty finance firm that provides senior ... today announced the closing of a $20 million ... a privately-held orthobiologics company engaged in the development ... the treatment of orthopedic injuries. Cerapedics, ...
Breaking Biology Technology: