Toggle Main Menu Toggle Search

Open Access padlockePrints

Inhibitors of both the N-methyl lysyl- and arginyl-demethylase activities of the JmjC oxygenases

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.

Publication metadata

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

Year: 2018

Volume: 373

Issue: 1748

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


DOI: 10.1098/rstb.2017.0071

PubMed id: 29685975


Altmetrics provided by Altmetric


Funder referenceFunder name
Wellcome Trust