RB1 methylation by SMYD2 enhances cell cycle progression through an increase of RB1 phosphorylation

Hyun Soo Cho, Shinya Hayami, Gouji Toyokawa, Kazuhiro Maejima, Yuka Yamane, Takehiro Suzuki, Naoshi Dohmae, Masaharu Kogure, Daechun Kang, David E. Neal, Bruce A.J. Ponder, Hiroki Yamaue, Yusuke Nakamura, Ryuji Hamamoto

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It is well known that RB functions are regulated by posttranslational modifications such as phosphorylation and acetylation, but the significance of lysine methylation on RB has not been fully elucidated. Our expression analysis of SMYD2 by quantitative real-time polymerase chain reaction showed that expression levels of SMYD2 are significantly elevated in human bladder carcinomas compared with nonneoplastic bladder tissues (P <.0001), and its expression levels in tumor tissues were much higher than those of any other normal tissues. SMYD2 knockdown resulted in the suppression of cancer cell growth, and cell cycle analysis indicated that SMYD2 might play a crucial role in the G1/S transition. According to an in vitro methyltransferase assay, we found that SMYD2 methylates RB1 protein, and liquid chromatography-tandem mass spectrometry analysis revealed lysine 810 of RB1 to be methylated by SMYD2. Importantly, this methylation enhanced Ser 807/811 phosphorylation of RB1 both in vitro and in vivo. Furthermore, we demonstrated that methylated RB1 accelerates E2F transcriptional activity and promotes cell cycle progression. SMYD2 is an important oncoprotein in various types of cancer, and SMYD2-dependent RB1 methylation at lysine 810 promotes cell cycle progression of cancer cells. Further study may explore SMYD2-dependent RB1 methylation as a potential therapeutic target in human cancer.

元の言語英語
ページ(範囲)476-486
ページ数11
ジャーナルNeoplasia (United States)
14
発行部数6
DOI
出版物ステータス出版済み - 6 2012

All Science Journal Classification (ASJC) codes

  • Cancer Research

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    Cho, H. S., Hayami, S., Toyokawa, G., Maejima, K., Yamane, Y., Suzuki, T., Dohmae, N., Kogure, M., Kang, D., Neal, D. E., Ponder, B. A. J., Yamaue, H., Nakamura, Y., & Hamamoto, R. (2012). RB1 methylation by SMYD2 enhances cell cycle progression through an increase of RB1 phosphorylation. Neoplasia (United States), 14(6), 476-486. https://doi.org/10.1593/neo.12656