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An Integrative Proteomic Approach Identifies Novel Cellular SMYD2 Substrates
Hazem Ahmed1, Shili Duan2, Cheryl H Arrowsmith1,2
1Structural Genomics Consortium, University of Toronto , 101 College Street, MaRS Centre, South Tower, Toronto, Ontario M5G 1L7, Canada.
Journal of Proteome Research
|May 11, 2016
Summary
This study introduces a bioinformatics method to discover new protein methylation targets for the SMYD2 enzyme. Six novel substrates were confirmed, advancing our understanding of lysine methylation in biological signaling.
Area of Science:
- Biochemistry
- Molecular Biology
- Proteomics
Background:
- Protein methylation is a crucial post-translational modification regulating gene expression and cellular functions.
- The specific interactions between human protein methyltransferases and their substrates are not well-defined.
- Understanding these interactions is key to deciphering complex cellular signaling pathways.
Purpose of the Study:
- To develop and apply a bioinformatics approach for identifying novel substrates of the lysine methyltransferase SMYD2.
- To experimentally validate the predicted SMYD2 substrates in a cellular context.
- To explore the potential of this integrative method for other protein lysine methyltransferases.
Main Methods:
- Integration of structural, biochemical, cellular, and proteomic data.
- Bioinformatic analysis to predict novel SMYD2 substrates.
- Experimental validation using immunoprecipitation and a selective SMYD2 inhibitor (BAY-598).
Main Results:
- Identification of 14 novel putative SMYD2 substrates.
- Experimental confirmation of six substrates: MAPT, CCAR2, EEF2, NCOA3, STUB1, and UTP14A.
- Demonstration that substrate methylation is dependent on SMYD2 catalytic activity, as shown by inhibitor treatment.
Conclusions:
- The developed integrative bioinformatics approach successfully identified and validated novel SMYD2 substrates.
- This methodology can be extended to investigate other protein lysine methyltransferases.
- The findings contribute to a better understanding of the role of lysine methylation in broader cellular signaling processes.
