Semi-Quantitative Mass Spectrometry in AML Cells Identifies New Non-Genomic Targets of the EZH2 Methyltransferase.
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.
Collections
Subject
Cell Line, Tumor
HL-60 Cells
Humans
Carrier Proteins
Histones
Protein Interaction Mapping
Computational Biology
Amino Acid Sequence
Protein Conformation
Protein Binding
Methylation
Models, Molecular
Mass Spectrometry
Leukemia, Myeloid, Acute
Workflow
Protein Interaction Maps
Gene Ontology
Enhancer of Zeste Homolog 2 Protein
Research team
Cancer Biomarkers
Paediatric Solid Tumour Biology and Therapeutics
Language
eng
Date accepted
2017-06-29
License start date
2017-07-05
Citation
International journal of molecular sciences, 2017, 18 (7)
Publisher
MDPI
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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