Dataset Information

Novel insights into histone lysine methyltransferases in cancer therapy: From epigenetic regulation to selective drugs.

ABSTRACT: The reversible and precise temporal and spatial regulation of histone lysine methyltransferases (KMTs) is essential for epigenome homeostasis. The dysregulation of KMTs is associated with tumor initiation, metastasis, chemoresistance, invasiveness, and the immune microenvironment. Therapeutically, their promising effects are being evaluated in diversified preclinical and clinical trials, demonstrating encouraging outcomes in multiple malignancies. In this review, we have updated recent understandings of KMTs' functions and the development of their targeted inhibitors. First, we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis, tumor suppression, and immune regulation. In addition, we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors. In summary, we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers.

SUBMITTER: Liao Q

PROVIDER: S-EPMC9999304 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Novel insights into histone lysine methyltransferases in cancer therapy: From epigenetic regulation to selective drugs.

Liao Qili Q Yang Jie J Ge Shengfang S Chai Peiwei P Fan Jiayan J Jia Renbing R

Journal of pharmaceutical analysis 20221130 2

The reversible and precise temporal and spatial regulation of histone lysine methyltransferases (KMTs) is essential for epigenome homeostasis. The dysregulation of KMTs is associated with tumor initiation, metastasis, chemoresistance, invasiveness, and the immune microenvironment. Therapeutically, their promising effects are being evaluated in diversified preclinical and clinical trials, demonstrating encouraging outcomes in multiple malignancies. In this review, we have updated recent understan ...[more]

PMID: 36908859

Similar Datasets

Project description:Dynamic histone lysine methylation, regulated by methyltransferases and demethylases, plays fundamental roles in chromatin structure and gene expression in a wide range of eukaryotic organisms. A large number of SET-domain-containing proteins make up the histone lysine methyltransferase (HKMT) family, which catalyses the methylation of different lysine residues with relatively high substrate specificities. Another large family of Jumonji C (JmjC)-domain-containing histone lysine demethylases (JHDMs) reverses histone lysine methylation with both lysine site and methyl-state specificities. Through bioinformatic analysis, at least nine SET-domain-containing genes were found in the malaria parasite Plasmodium falciparum and its sibling species. Phylogenetic analysis separated these putative HKMTs into five subfamilies with different putative substrate specificities. Consistent with the phylogenetic subdivision, methyl marks were found on K4, K9 and K36 of histone H3 and K20 of histone H4 by site-specific methyl-lysine antibodies. In addition, most SET-domain genes and histone methyl-lysine marks displayed dynamic changes during the parasite asexual erythrocytic cycle, suggesting that they constitute an important epigenetic mechanism of gene regulation in malaria parasites. Furthermore, the malaria parasite and other apicomplexan genomes also encode JmjC-domain-containing proteins that may serve as histone lysine demethylases. Whereas prokaryotic expression of putative active domains of four P. falciparum SET proteins did not yield detectable HKMT activity towards recombinant P. falciparum histones, two protein domains expressed in vitro in a eukaryotic system showed HKMT activities towards H3 and H4, respectively. With the discovery of these Plasmodium SET- and JmjC-domain genes in the malaria parasite genomes, future efforts will be directed towards elucidation of their substrate specificities and functions in various cellular processes of the parasites.

Dataset Information

Novel insights into histone lysine methyltransferases in cancer therapy: From epigenetic regulation to selective drugs.

Publications

Novel insights into histone lysine methyltransferases in cancer therapy: From epigenetic regulation to selective drugs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets