Enhanced HSP70 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 and Ryuji Hamamoto ()
Additional contact information
Hyun-Soo Cho: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo
Tadahiro Shimazu: Chemical Genomics Research Group, RIKEN Advanced Science Institute
Gouji Toyokawa: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo
Yataro Daigo: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo
Yoshihiko Maehara: Graduate School of Medical Science, Kyushu University
Shinya Hayami: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo
Akihiro Ito: Chemical Genomics Research Group, RIKEN Advanced Science Institute
Ken Masuda: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo
Noriko Ikawa: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo
Helen I. Field: University of Cambridge
Eiju Tsuchiya: Saitama Cancer Center
Shin-ichi Ohnuma: Institute of Ophthalmology, University College London
Bruce A.J. Ponder: Cancer Research UK Cambridge Research Institute, University of Cambridge
Minoru Yoshida: Chemical Genomics Research Group, RIKEN Advanced Science Institute
Yusuke Nakamura: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo
Ryuji Hamamoto: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo

Nature Communications, 2012, vol. 3, issue 1, 1-10

Abstract: Abstract 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.

Date: 2012
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DOI: 10.1038/ncomms2074

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