Enhanced HSP70Â lysine methylation promotes proliferation of cancer cells through activation of Aurora kinase B

Hyun Soo Cho, Tadahiro Shimazu, Gouji Toyokawa, Yataro Daigo, Yoshihiko Maehara, Shinya Hayami, Akihiro Ito, Ken Masuda, Noriko Ikawa, Helen I. Field, Eiju Tsuchiya, Shin Ichi Ohnuma, Bruce A.J. Ponder, Minoru Yoshida, Yusuke Nakamura, Ryuji Hamamoto

研究成果: Contribution to journalArticle査読

82 被引用数 (Scopus)

抄録

Although heat-shock protein 70 (HSP70), an evolutionarily highly conserved molecular chaperone, is known to be post-translationally modified in various ways such as phosphorylation, ubiquitination and glycosylation, physiological significance of lysine methylation has never been elucidated. Here we identify dimethylation of HSP70 at Lys-561 by SETD1A. Enhanced HSP70 methylation was detected in various types of human cancer by immunohistochemical analysis, although the methylation was barely detectable in corresponding non-neoplastic tissues. Interestingly, methylated HSP70 predominantly localizes to the nucleus of cancer cells, whereas most of the HSP70 protein locates to the cytoplasm. Nuclear HSP70 directly interacts with Aurora kinase B (AURKB) in a methylation-dependent manner and promotes AURKB activity in vitro and in vivo. We also find that methylated HSP70 has a growth-promoting effect in cancer cells. Our findings demonstrate a crucial role of HSP70 methylation in human carcinogenesis.

本文言語英語
論文番号1072
ジャーナルNature communications
3
DOI
出版ステータス出版済み - 2012

All Science Journal Classification (ASJC) codes

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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