Recent developments in catalysis and inhibition of the Jumonji histone demethylases.

Autor: Sarah L; Chemistry and Chemical Biology Graduate Program, University of California San Francisco; San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California San Francisco; San Francisco, CA 94158, USA., Fujimori DG; Department of Cellular and Molecular Pharmacology, University of California San Francisco; San Francisco, CA 94158, USA; Department of Pharmaceutical Chemistry, University of California San Francisco; San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California San Francisco; San Francisco, CA 94158, USA. Electronic address: danica.fujimori@ucsf.edu.
Jazyk: angličtina
Zdroj: Current opinion in structural biology [Curr Opin Struct Biol] 2023 Dec; Vol. 83, pp. 102707. Date of Electronic Publication: 2023 Oct 11.
DOI: 10.1016/j.sbi.2023.102707
Abstrakt: Histone methylation, one of the most common histone modifications, has fundamental roles in regulating chromatin-based processes. Jumonji histone lysine demethylases (JMJC KDMs) influence regulation of gene transcription through both their demethylation and chromatin scaffolding functions. It has recently been demonstrated that dysregulation of JMJC KDMs contributes to pathogenesis and progression of several diseases, including cancer. These observations have led to an increased interest in modulation of enzymes that regulate lysine methylation. Here, we highlight recent progress in understanding catalysis of JMJC KDMs. Specifically, we focus on recent research advances on elucidation of JMJC KDM substrate recognition and interactomes. We also highlight recently reported JMJC KDM inhibitors and describe their therapeutic potentials and challenges. Finally, we discuss alternative strategies to target these enzymes, which rely on targeting JMJC KDMs accessory domains as well as utilization of the targeted protein degradation strategy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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