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Lookup NU author(s): Professor Akane Kawamura
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2018 The Authors. The Jumonji C (JmjC) family of 2-oxoglutarate (2OG)-dependent oxygenases have established roles in the regulation of transcription via the catalysis of demethylation of Ne-methylated lysine residues in histone tails, especially the N-terminal tail of histone H3. Most human JmjC N ε -methyl lysine demethylases (KDMs) are complex enzymes, with ‘reader domains’ in addition to their catalytic domains. Recent biochemical evidence has shown that some, but not all, JmjC KDMs also have Nω-methyl arginyl demethylase (RDM) activity. JmjC KDM activity has been linked to multiple cancers and some JmjC proteins are therapeutic targets. It is, therefore, important to test not only whether compounds in development inhibit the KDM activity of targeted JmjC demethylases, but also whether they inhibit other activities of these proteins. Here we report biochemical studies on the potential dual inhibition of JmjC KDM and RDM activities using a model JmjC demethylase, KDM4E (JMJD2E). The results reveal that all of the tested compounds inhibit both the KDM and RDM activities, raising questions about the in vivo effects of the inhibitors.
Author(s): Bonnici J, Tumber A, Kawamura A, Schofield CJ
Publication type: Article
Publication status: Published
Journal: Philosophical Transactions of the Royal Society B: Biological Sciences
Online publication date: 23/04/2018
Acceptance date: 03/10/2017
Date deposited: 14/10/2019
ISSN (print): 0962-8436
ISSN (electronic): 1471-2970
Publisher: Royal Society Publishing
PubMed id: 29685975
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