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Protein wields phosphate group to inhibit cancer metastasis
Date:1/3/2011

osphorylation trumping methylation, Hung said. The phosphorylated version of EZH2 cannot methylate the target histone protein, so repressed genes are awakened.

Cancer cells with EZH2 that had a mutant version of the location where the phosphate group connects, preventing phosphorylation, had double the cell migration and invasion of cancer cells with the regular, unmutated version of EZH2.

Same process vital to bone formation

EZH2 plays an important normal role in a variety of biological processes. "EZH2 is crucial to embryonic development because it turns genes off and on to guide the differentiation of embryonic stem cells into tissues and organs," Hung said. Embryonic stem cells can turn into any type of cell.

In a separate set of experiments, the researchers demonstrated that phosphorylation of EZH2 is necessary to the production of bone cells (osteoblasts).

Mesenchymal stem cells can differentiate into bone, cartilage or fat cells. The team showed only those cells with EZH2 phosphorylated by CDK1 differentiated into bone cells. Genes crucial to bone formation were silenced by methlyation but awakened when CDK1 altered EZH2.

A genomewide screen to identify genes targeted by EZH2 in mesenchymal stem cells was conducted before and after the cells differentiated into bone cells. Before, more than 4,000 genes were found to bind to EZH2. After differentiation to bone cells, 30 or fewer genes bound to the protein.

"This and other recently reported studies open up drug development possibilities by either inhibiting the methyltransferase activity of EZH2 or regulating phosphorylation to indirectly regulate EZH2's activity," Hung said.

"This study also suggests a possible way to induce mesenchymal stem cell differentiation into bone cells, which may have long-term implications for regenerative medicine for bone disease," Hung said.


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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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