Priority Research Papers:
SUV420H1 enhances the phosphorylation and transcription of ERK1 in cancer cells
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Theodore Vougiouklakis1,*, Kenbun Sone1,*, Vassiliki Saloura1, Hyun-Soo Cho1, Takehiro Suzuki2, Naoshi Dohmae2, Houda Alachkar1, Yusuke Nakamura1, Ryuji Hamamoto1
1Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
2Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan
*These authors contributed equally to this work
Ryuji Hamamoto, e-mail: [email protected]
Keywords: ERK1, SUV420H1, protein lysine methyltransferase, non-histone protein methylation
Received: September 07, 2015 Accepted: November 11, 2015 Published: November 19, 2015
The oncogenic protein ERK, a member of the extracellular signal-regulated kinase (ERK) cascade, is a well characterized signaling molecule involved in tumorigenesis. The ERK signaling pathway is activated in a large proportion of cancers and plays a critical role in tumor development. Functional regulation by phosphorylation of kinases in the ERK pathway has been extensively studied, however methylation of the ERK protein has not been reported to date. Here, we demonstrated that the protein lysine methyltransferase SUV420H1 tri-methylated ERK1 at lysines 302 and 361, and that substitution of methylation sites diminished phosphorylation levels of ERK1. Concordantly, knockdown of SUV420H1 reduced phosphorylated ERK1 and total ERK1 proteins, and interestingly suppressed ERK1 at the transcriptional level. Our results indicate that overexpression of SUV420H1 may result in activation of the ERK signaling pathway through enhancement of ERK phosphorylation and transcription, thereby providing new insights in the regulation of the ERK cascade in human cancer.
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