title: SUV420H1 enhances the phosphorylation and transcription of ERK1 in cancer cells.
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.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Theodore
authors.initials: T
authors.lastname: Vougiouklakis
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Kenbun
authors.initials: K
authors.lastname: Sone
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Saloura
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Cho
authors.affiliation: Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Houda
authors.initials: H
authors.lastname: Alachkar
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hamamoto
mesh_terms: D015153:Blotting, Western; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D013058:Mass Spectrometry; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis*; D009369:Neoplasms / Q000473:pathology*; D010766:Phosphorylation; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D011495:Histone-Lysine N-Methyltransferase; C542918:KMT5C protein, human; D048052:Mitogen-Activated Protein Kinase 3
keywords: ERK1; SUV420H1; non-histone protein methylation; protein lysine methyltransferase