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Involvement of heat-shock protein 90 in the interleukin-6-mediated signaling pathway through STAT3.

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Title: Involvement of heat-shock protein 90 in the interleukin-6-mediated signaling pathway through STAT3.
Authors: Sato, Noriko Browse this author
Yamamoto, Tetsuya Browse this author
Sekine, Yuichi Browse this author
Yumioka, Taro Browse this author
Junicho, Akira Browse this author
Fuse, Hideki Browse this author
Matsuda, Tadashi Browse this author →KAKEN DB
Keywords: IL-6
Heat-shock protein 90
Signal transducer and activator of transcription
Issue Date: 24-Jan-2003
Publisher: Elsevier
Journal Title: Biochemical and Biophysical Research Communications
Volume: 300
Issue: 4
Start Page: 847
End Page: 852
Publisher DOI: 10.1016/S0006-291X(02)02941-8
PMID: 12559950
Abstract: Interleukin-6 (IL-6) is a multifunctional cytokine playing roles in the immune system, hematopoiesis, and acute phase reactions. IL-6 also regulates the growth of various types of human malignant tumors. Here we demonstrate that IL-6-induced gene expression was suppressed by a specific heat-shock protein 90 (Hsp90) inhibitor, geldanamycin (GA) in human hepatoma Hep3B cells. GA also suppressed the IL-6-induced activation of signal transducer and activator of transcription 3 (STAT3) in a human embryonic kidney carcinoma 293T cells. This inhibitory effect of GA on STAT3 activation was reversed by overexpression of Hsp90. Furthermore, Hsp90 directly bound to STAT3 via its N-terminal region, which interacted with GA. We provide evidence that the action of GA on IL-6 functions was due to the inhibition of direct physical interactions between STAT3 and Hsp90, which represents a novel role of Hsp90 in the IL-6 signaling pathways.
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 松田 正

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