A lot of efforts are made to identify potent and selective inhibitors for the demethylation reactions catalyzed by members of the JMJD2 and JARID1 protein families (1, 2). Both epigenetic eraser enzyme families have been discussed as potential cancer therapeutic targets. In this post, I will review the last releases regarding JMJD2 and JARID1 protein families for assay development and drug discovery applications.
JMJD2 (Jumonji domain-containing protein 2) and JARID1 (Jumonji, AT rich interactive domain 1) belong to the Nε-trimethyl-lysine demethylases. They demethylate Histones in an iron(II) and -ketoglutarate-dependent reaction (3).
JARID1 demethylases (belonging to the KDM5 family) act on trimethylated lysine K4 in histone H3 (H3K4me3). This family consists of JARID1A (or KDM5A or RBP2), JARID1B (or KDM5B or PLU1), JARID1C (or KDM5C or SMCX), and JARID1D (or KDM5D or SMCY) (2). JARID1 demethylases have been associated to diseases such as cancer and mental retardation. Both JARID1A and JARID1B are potential oncoproteins, and overexpressed in a variety of cancers (4). Furthermore, increased JARID1A expression leads to a more stem-like phenotype and enhanced resistance to anticancer agents (5).
JMJD2 enzymes (belonging to the KDM4 family of demethylases) act on di- and trimethylated H3K9, H3K36, and H1K26. The family consists of JMJD2A (or KDM4A), JMJD2B (or KDM4B), JMJD2C (or KDM4C), JMJD2D (or KDM4D), and JMJD2E (or KDM4DL). JMJD2A, JMJD2B, and JMJD2C have been shown to be overexpressed in breast, colorectal, lung, prostate, and other tumors and are required for efficient cancer cell growth. It has been assumed that this is due to their ability to modulate transcription factors such as the androgen and estrogen receptor (6).
8 new ready-to-use JMJD2 & JARID1 assays
Recently, a few ready-to-use JMJD2 & JARID1 related research tools have been made available to the research community.
Here is my selection of BPS Biosciences‘s novelties to screen JMJD2 & JARID1 inhibitors:
Our partner BPS Biosciences developed ready to use kits to screen for inhibitors of both demethylase types:
- JARID1A assay kits
- JARID1B assay kit
- JARID1C assay kit
- JMJD2A assay kit
- JMJD2B assay kit
- JMJD2C assay kits
- JMJD2D assay kit
- JMJD2E assay kit
Of course you might also need active enzymes and/or substrates for epigenetic assay development, of which a wide variety are also available. Research tools reviewed in this post can definitely help you in your epigenetic research – in drug discovery activities and screening for inhibitors of epigenetic target enzymes and in academic and fundamental research as well.
- Zeng and Huang, Med. Chem. Commun. 5, 297-313 (2014)
- Sayegh et al., J. Biol. Chem. 288, 13, 9408–17 (2013)
- Klose and Zhang, Nat. Rev. Mol. Cell Biol. 8, 307–18 (2007)
- Blair et al., Cancers 3, 1383–1404 (2011)
- Sharmaet al., Cell 141, 69–80 (2010)
- Berry and Janknecht, Cancer Res 73, 10 (2013)
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