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

被引：97

作者：

Cho, Hyun-Soo ^{[1
]}

Shimazu, Tadahiro ^{[2
]}

Toyokawa, Gouji ^{[1
,3
]}

Daigo, Yataro ^{[1
,4
]}

Maehara, Yoshihiko ^{[3
]}

Hayami, Shinya ^{[1
]}

Ito, Akihiro ^{[2
]}

Masuda, Ken ^{[1
]}

Ikawa, Noriko ^{[1
]}

Field, Helen I. ^{[5
]}

Tsuchiya, Eiju ^{[6
,7
]}

Ohnuma, Shin-ichi ^{[8
]}

Ponder, Bruce A. J. ^{[9
]}

Yoshida, Minoru ^{[2
]}

Nakamura, Yusuke ^{[1
,10
]}

Hamamoto, Ryuji ^{[1
,9
]}

机构：

[1] Univ Tokyo, Mol Med Lab, Ctr Human Genome, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan

[2] RIKEN Adv Sci Inst, Chem Genom Res Grp, Wako, Saitama 3510198, Japan

[3] Kyushu Univ, Dept Surg & Sci, Grad Sch Med Sci, Higashi Ku, Fukuoka 8128582, Japan

[4] Shiga Univ Med Sci, Dept Med Oncol, Otsu, Shiga 5202192, Japan

[5] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England

[6] Saitama Canc Ctr, Dept Pathol, Ina, Saitama 3620806, Japan

[7] Kanagawa Canc Ctr, Res Inst, Mol Pathol & Genet Div, Yokohama, Kanagawa 2410815, Japan

[8] UCL, Inst Ophthalmol, London EC1V 9EL, England

[9] Univ Cambridge, Dept Oncol, Canc Res UK Cambridge Res Inst, Cambridge CB2 0RE, England

[10] Univ Chicago, Sect Hematol Oncol, Chicago, IL 60637 USA

来源：

NATURE COMMUNICATIONS | 2012年 / 3卷

基金：

日本学术振兴会;

关键词：

HUMAN CARCINOGENESIS; THERAPEUTIC TARGET; HISTONE H3; MITOTIC PHOSPHORYLATION; CHROMOSOMAL PASSENGERS; EXPRESSION PROFILES; LUNG CANCERS; P53; ACTIVITY; SURVIVIN; ARGININE;

D O I：

10.1038/ncomms2074

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

共 51 条

[51] Dysregulation of PRMT1 and PRMT6, Type I arginine methyltransferases, is involved in various types of human cancers [J].

Yoshimatsu, Masanori ;

Toyokawa, Gouji ;

Hayami, Shinya ;

Unoki, Motoko ;

Tsunoda, Tatsuhiko ;

Field, Helen I. ;

Kelly, John D. ;

Neal, David E. ;

Maehara, Yoshihiko ;

Ponder, Bruce A. J. ;

Nakamura, Yusuke ;

Hamamoto, Ryuji .

INTERNATIONAL JOURNAL OF CANCER, 2011, 128 (03) :562-573

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