Segregating out UbcH10's role in tumor formation

Jan 11, 2010
A single chromosome lags behind the others in a dividing cell overexpressing UbcH10. Credit: van Ree, J.H., et al. 2010. J. Cell Biol. doi:10.1083/jcb.200906147

A ubiquitin-conjugating enzyme that regulates the cell cycle promotes chromosome missegregation and tumor formation, according to van Ree et al. in the January 11 issue of the Journal of Cell Biology.

The mitotic E2 enzyme UbcH10 partners with the anaphase-promoting complex/cyclosome (APC/C) to ubiquitinate cell cycle regulators, targeting them for proteasomal destruction, and ensuring progression through mitosis. UbcH10 is overexpressed in a variety of human cancers, but whether it causes tumors or is simply up-regulated due to the increased number of proliferating cancer cells is unknown.

van Ree et al. generated mice expressing high levels of UbcH10 and found that they formed tumors in a broad range of tissues. Many of these tumors displayed aneuploidy—abnormal numbers of resulting from errors in cell division. Live microscopy showed that cells expressing high amounts of UbcH10 had problems segregating sister chromatids correctly, possibly because the cells contained extra numbers of centrosomes that might complicate formation of a normal mitotic spindle. UbcH10 overexpression also reduced levels of the mitotic regulator cyclinB—a substrate of the APC/C—though it remains to be seen if this contributes directly to centrosome amplification and aneuploidy.

The same research group recently demonstrated that chromosome segregation defects drive tumorigenesis by promoting the loss of tumor suppressor genes like . Senior author Jan van Deursen now wants to investigate whether UbcH10 synergizes with other factors to promote chromosome instability in human cancers.

Explore further: AstraZeneca cancer drug, companion test approved

More information: van Ree, J.H., et al. 2010. J. Cell Biol. doi:10.1083/jcb.200906147

add to favorites email to friend print save as pdf

Related Stories

Researchers prove key cancer theory

Dec 07, 2009

Mayo Clinic researchers have proven the longstanding theory that changes in the number of whole chromosomes -- called aneuploidy -- can cause cancer by eliminating tumor suppressor genes. Their findings, which appear in the ...

Researchers identify potential cancer target

Jan 16, 2009

(PhysOrg.com) -- Dartmouth Medical School researchers have found two proteins that work in concert to ensure proper chromosome segregation during cell division. Their study is in the January 2009 issue of ...

Researchers shed light on how tumor cells form

Jun 21, 2006

MIT cancer researchers have discovered a process that may explain how some tumor cells form, a discovery that could one day lead to new therapies that prevent defective cells from growing and spreading.

Recommended for you

Putting the brakes on cancer

13 hours ago

A study led by the University of Dundee, in collaboration with researchers at our University, has uncovered an important role played by a tumour suppressor gene, helping scientists to better understand how ...

Peanut component linked to cancer spread

14 hours ago

Scientists at the University of Liverpool have found that a component of peanuts could encourage the spread and survival of cancer cells in the body.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.