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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

Item Type: Article

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.

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More Information

Depositing User: Kevin Petrie

Identifiers

Item ID: 12449
Identification Number: https://doi.org/10.3390/ijms18071440
ISSN: 1422-0067
URI: http://sure.sunderland.ac.uk/id/eprint/12449
Official URL: https://www.mdpi.com/1422-0067/18/7/1440

Users with ORCIDS

ORCID for Kevin Petrie: ORCID iD orcid.org/0000-0002-9805-9152

Catalogue record

Date Deposited: 18 Aug 2020 19:23
Last Modified: 30 Sep 2020 10:49

Contributors

Author: Kevin Petrie ORCID iD
Author: Yordan Sbirkov
Author: Colin Kwok
Author: Amandeep Bhamra
Author: Andrew J Thompson
Author: Veronica Gil
Author: Arthur Zelent

University Divisions

Faculty of Health Sciences and Wellbeing > School of Medicine

Subjects

Sciences > Biomedical Sciences
Sciences > Health Sciences

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