SUV420H1 enhances the phosphorylation and transcription of ERK1 in cancer cells

// Theodore Vougiouklakis 1, * , Kenbun Sone 1, * , Vassiliki Saloura 1 , Hyun-Soo Cho 1 , Takehiro Suzuki 2 , Naoshi Dohmae 2 , Houda Alachkar 1 , Yusuke Nakamura 1 , Ryuji Hamamoto 1 1 Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA 2 Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan * These authors contributed equally to this work Correspondence to: Ryuji Hamamoto, e-mail: rhamamoto@medicine.bsd.uchicago.edu Keywords: ERK1, SUV420H1, protein lysine methyltransferase, non-histone protein methylation Received: September 07, 2015      Accepted: November 11, 2015      Published: November 19, 2015 ABSTRACT 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.