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

By Hyun-soo Cho, Tadahiro Shimazu, G. Toyokawa, Y. Daigo, Yoshihiko Maehara, S. Hayami, A. Ito, K. Masuda, Noriko Ikawa, Helen I. Field and 6 more. 2012

120 citations recorded by the source corpus.

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. HSP70 is a molecular chaperone that aids protein folding. In this study, HSP70 is shown to be methylated and this post-translationally modified protein is elevated in expression in human cancers and promotes the activity of Aurora kinase B.

Subfields: Cell Biology, Materials Chemistry, Molecular Biology

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Citations in the corpus

Dysregulation of AKT Pathway by SMYD2-Mediated Lysine Methylation on PTEN (2015, methodology): “In Vitro Methyltransferase Assay In vitro methyltransferase assays were described previously [17,19–22].”
Late Cornified Envelope Group I, a Novel Target of p53, Regulates PRMT5 Activity (2014, background): “Current progress of molecular medicine revealed that the enzymes relevant to histonemethylation play critical roles in human carcinogenesis [28,35–45].”
The novel prognostic marker, EHMT2, is involved in cell proliferation via HSPD1 regulation in breast cancer (2018, background): “Regarding re‐localization, Cho et al reported that methylation of HSP70 by SETD1A changes its location from the cytoplasm to the nucleus (27).”
SMYD2-dependent HSP90 methylation promotes cancer cell proliferation by regulating the chaperone complex formation. (2014, methodology): “293T cells were co-transfected with a FLAGSMYD2 expression vector and four different lengths of HA-HSP90AB1 vectors ([1–724], [1–500], [250–724] and [500–724]).”
PRMT1 promotes mitosis of cancer cells through arginine methylation of INCENP (2015, methodology): “In vitro methyltransferase assays were described previously [37, 39-46].”
The histone methyltransferase SMYD2 methylates PARP1 and promotes poly(ADP-ribosyl)ation activity in cancer cells. (2014, methodology): “After boiling in sample buffer, the samples were subjected to SDS-PAGE, and visualized by fluorography [34].”
SUV39H2 methylates and stabilizes LSD1 by inhibiting polyubiquitination in human cancer cells (2015, methodology): “In vitro methyltransferase assays were performed as described previously [7, 44-50].”