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Enhanced HSP70 lysine methylation promotes proliferation of cancer cells through activation of Aurora kinase B

Author

Listed:
  • 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
    Graduate School of Medical Science, Kyushu University)

  • Yataro Daigo

    (Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo
    Shiga University of Medical Science)

  • 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
    Kanagawa Cancer Center Research Institute)

  • 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
    Section of Hematology/Oncology, The University of Chicago)

  • Ryuji Hamamoto

    (Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo
    Cancer Research UK Cambridge Research Institute, University of Cambridge)

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.

Suggested Citation

  • 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 & Bruc, 2012. "Enhanced HSP70 lysine methylation promotes proliferation of cancer cells through activation of Aurora kinase B," Nature Communications, Nature, vol. 3(1), pages 1-10, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2074
    DOI: 10.1038/ncomms2074
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