3 research outputs found
An Integrative Proteomic Approach Identifies Novel Cellular SMYD2 Substrates
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
An Integrative Proteomic Approach Identifies Novel Cellular SMYD2 Substrates
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