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Abstract:
Histone demethylases are a newly discovered class of non-heme iron enzymes that play an important role in regulating transcription and epigenetic inheritance. We have successfully expressed and purified highly active histone demethylases (HDMs), including the cancer-relevant JMJD2C (GASC1). A detailed enzyme kinetic and inhibition analysis of these HDMs was achieved through a range of fluorescence assays, mass spectrometry, and oxygen consumption measurements. An interesting case of cosubstrate inhibition is observed for these HDMs. We have also started to develop specific inhibitors for these enzymes using an enzyme-templated approach that takes advantage of the enzyme s substrate specificity. The identified inhibitors will be tested for the inhibition of JMJD2C in MCF7 breast cancer cells. The developed specific inhibitors could lead to novel breast cancer therapeutics and can also be used as tools for studying the role of histone demethylases in breast cancer cell proliferation.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual rept. 1 Aug 2010-31 Jul 2011 |
| Pages: |
19 |
| Report Date: |
Aug 2011 |
| Contract Number: |
W81XWH-10-1-0442 |
| Report Number: |
A810455 |
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