Document Detail


Enhanced HSP70 lysine methylation promotes proliferation of cancer cells through activation of Aurora kinase B.
MedLine Citation:
PMID:  22990868     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature communications     Volume:  3     ISSN:  2041-1723     ISO Abbreviation:  Nat Commun     Publication Date:  2012  
Date Detail:
Created Date:  2012-09-19     Completed Date:  2013-02-01     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101528555     Medline TA:  Nat Commun     Country:  England    
Other Details:
Languages:  eng     Pagination:  1072     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
COS Cells
Cell Line, Tumor
Cell Proliferation
Cercopithecus aethiops
HSP70 Heat-Shock Proteins / metabolism*
Humans
Immunohistochemistry
Immunoprecipitation
Lysine
Methylation
Protein Binding
Protein-Serine-Threonine Kinases / metabolism*
Tissue Array Analysis
Chemical
Reg. No./Substance:
0/HSP70 Heat-Shock Proteins; 56-87-1/Lysine; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/aurora kinase
Comments/Corrections

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