Semi-Quantitative Mass Spectrometry in AML Cells Identifies New Non-Genomic Targets of the EZH2 Methyltransferase.

Sbirkov, Yordan, Kwok, Colin, Bhamra, Amandeep, Thompson, Andrew J, Gil, Veronica, Zelent, Arthur and Petrie, Kevin (2017) Semi-Quantitative Mass Spectrometry in AML Cells Identifies New Non-Genomic Targets of the EZH2 Methyltransferase. International journal of molecular sciences, 18 (7). ISSN 1422-0067

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Abstract

Alterations to the gene encoding the EZH2 (KMT6A) methyltransferase, including both gain-of-function and loss-of-function, have been linked to a variety of haematological malignancies and solid tumours, suggesting a complex, context-dependent role of this methyltransferase. The successful implementation of molecularly targeted therapies against EZH2 requires a greater understanding of the potential mechanisms by which EZH2 contributes to cancer. One aspect of this effort is the mapping of EZH2 partner proteins and cellular targets. To this end we performed affinity-purification mass spectrometry in the FAB-M2 HL-60 acute myeloid leukaemia (AML) cell line before and after all- retinoic acid-induced differentiation. These studies identified new EZH2 interaction partners and potential non-histone substrates for EZH2-mediated methylation. Our results suggest that EZH2 is involved in the regulation of translation through interactions with a number of RNA binding proteins and by methylating key components of protein synthesis such as eEF1A1. Given that deregulated mRNA translation is a frequent feature of cancer and that eEF1A1 is highly expressed in many human tumours, these findings present new possibilities for the therapeutic targeting of EZH2 in AML.

Item Type: Article
Subjects: Sciences > Biomedical Sciences
Sciences > Health Sciences
Divisions: Faculty of Health Sciences and Wellbeing > School of Medicine
Depositing User: Kevin Petrie
Date Deposited: 18 Aug 2020 19:23
Last Modified: 18 Aug 2020 19:23
URI: http://sure.sunderland.ac.uk/id/eprint/12449
ORCID for Kevin Petrie: ORCID iD orcid.org/0000-0002-9805-9152

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