期刊
JOURNAL OF PROTEOME RESEARCH
卷 15, 期 6, 页码 2052-2059出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.6b00220
关键词
SMYD2; non-histone substrates; lysine methylation; data integration; pan-methyl lysine antibody
资金
- AbbVie
- Bayer
- Boehringer Ingelheim
- Genome Canada through Ontario Genomics Institute [OGI-055]
- GlaxoSmithKline
- Janssen
- Lilly Canada
- Novartis Research Foundation
- Ontario Ministry of Economic Development and Innovation
- Pfizer
- Takeda
- Wellcome Trust [092809/Z/10/Z]
Protein methylation is a post-translational modification with important roles in transcriptional regulation and other biological processes, but the enzyme-substrate relationship between the 68 known human protein methyltransferases and the thousands of reported methylation sites is poorly understood. Here, we propose a bioinformatic approach that integrates structural, biochemical, cellular, and proteomic data to identify novel cellular substrates of the lysine methyltransferase SMYD2. Of the 14 novel putative SMYD2 substrates identified by our approach, six were confirmed in cells by immunoprecipitation: MAPT, CCAR2, EEF2, NCOA3, STUB1, and UTP14A. Treatment with the selective SMYD2 inhibitor BAY-598 abrogated the methylation signal, indicating that methylation of these novel substrates was dependent on the catalytic activity of the enzyme. We believe that our integrative approach can be applied to other protein lysine methyltransferases, and help understand how lysine methylation participates in wider signaling processes.
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