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Int. J. Mol. Sci. 2017, 18(7), 1440; doi:10.3390/ijms18071440

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

1
Theodor Boveri Institute and Comprehensive Cancer Center Mainfranken, Biocenter, University of Würzburg, Würzburg 97074, Germany
2
Division of Clinical Studies, Institute of Cancer Research, London SW7 3RP, UK
3
UCL Cancer Institute, Paul O’Gormon Building, London WC1E 6DD, UK
4
Proteomics and Metabolomics Core Facility, Institute of Cancer Research, London SW7 3RP, UK
5
Miller School of Medicine, University of Miami, Miami, FL 33136, USA
6
Faculty of Natural Sciences, University of Stirling, Stirling FK9 4LA, UK
*
Author to whom correspondence should be addressed.
Received: 10 June 2017 / Revised: 27 June 2017 / Accepted: 29 June 2017 / Published: 5 July 2017
(This article belongs to the Special Issue The Biology and Treatment of Myeloid Leukaemias)
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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-trans 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. View Full-Text
Keywords: acute myeloid leukaemia; EZH2; mass spectrometry; methylation; eEF1A1 acute myeloid leukaemia; EZH2; mass spectrometry; methylation; eEF1A1
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Sbirkov, Y.; Kwok, C.; Bhamra, A.; Thompson, A.J.; Gil, V.; Zelent, A.; Petrie, K. Semi-Quantitative Mass Spectrometry in AML Cells Identifies New Non-Genomic Targets of the EZH2 Methyltransferase. Int. J. Mol. Sci. 2017, 18, 1440.

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