Nav: Home

Harvard Medical School Researchers Identify Four Human Genes Essential To Cell Division; Discovery Yields New Target For Cancer Therapies

February 24, 1998

BOSTON--February 24, 1998--Researchers at Harvard Medical School have identified four human genes that serve a critical role in cell division. The findings provide a new target for anticancer agents, which may result in fewer therapeutic side-effects.

Hongtao Yu, a postdoctoral fellow in the laboratory of Marc Kirschner, the Carl W. Walter professor of cell biology at Harvard Medical School, and his colleagues used frog (Xenopus) protein sequences as a guide to identify the remaining four human genes in the eight-unit anaphase-promoting complex (APC). The APC's critical role in cell division makes it a perfect target for the fight against cancer, in which cells escape regulation and divide uncontrollably. The findings are published in the February 20 Science.

APC proteins are activated as the cell progresses through mitosis, but as yet, Kirschner and Yu do not know exactly how they are regulated. However, uncertainty about APC's regulation does not diminish the potential of this multi-subunit complex for anticancer therapeutics. With its seminal role in mitosis, the APC seems to be a perfect site to halt cell division. Like the anticancer drug Taxol that also disrupts mitosis, the advantage with an APC inhibitor would be preferential delivery to rapidly dividing tumor cells. "A lot of normal cells are just not dividing at all," says Yu. These law-abiding noncancerous cells would be invisible to the APC inhibitor, avoiding dangerous side effects that plague many anticancer drugs. The APC complex provides "a whole new set of targets which don't function at all in non-dividing cells," says Kirschner.

For successful cell division -- when the cytoplasmic and genetic contents of a cell are faithfully reproduced in the daughter progeny -- two cycles must be synchronized. The DNA is replicated in one cycle, and the chromosomes divide during mitosis -- the second cycle.

The APC is one of the mitotic ringleaders. "It is absolutely required for cell proliferation," says Yu. The protein complex drives a dividing cell from the metaphase stage of mitosis into anaphase--from the point in which the chromosomes find their partner and gather in pairs in the center of the cell, to the point in which each member of the chromosomal pair separates and migrates to the distant cellular poles. A new cell membrane forms between the chromosomal clumps, and mitosis concludes with the formation of two identical daughter cells, each containing an intact copy of the parent cell's genetic information.

An essential step in the development of any new drug is an accurate detection system that will report whether the compound being tested is having the desired effect on the target cell. If APC inhibition is detected following addition of a certain compound the chemical that sounded the alarm can be carefully investigated for its clinical suitability. The Kirschner group has filed a patent for the biochemical method that they devised for analyzing APC activity. The assay is amenable to automation, making it an attractive way to quickly screen many different chemical compounds.

"The intention is to use [the assay] to screen for small molecule inhibitors which might be very useful in anticancer and antiproliferation drugs," says Kirschner.

The study was funded by two grants from the National Institutes of Health.
-end-


Harvard Medical School

Related Cancer Articles:

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
More Cancer News and Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...