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: Theodore Vougiouklakis, Kenbun Sone, Vassiliki Saloura, Hyun-Soo Cho, Takehiro Suzuki, Naoshi Dohmae, Houda Alachkar, Yusuke Nakamura, Ryuji Hamamoto
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 41 Pg. 43162-71 (Dec 22 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26586479 (Publication Type: Journal Article)

Chemical References

• RNA, Small Interfering
• Histone-Lysine N-Methyltransferase
• KMT5C protein, human
• Mitogen-Activated Protein Kinase 3

Topics

• Blotting, Western
• Carcinogenesis (genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (physiology)
• Gene Expression Regulation, Neoplastic (physiology)
• Histone-Lysine N-Methyltransferase (metabolism)
• Humans
• MAP Kinase Signaling System (physiology)
• Mass Spectrometry
• Mitogen-Activated Protein Kinase 3 (biosynthesis)
• Neoplasms (pathology)
• Phosphorylation
• RNA, Small Interfering
• Real-Time Polymerase Chain Reaction
• Transcription, Genetic
• Transfection