2024-03-29T00:44:23Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/281212022-11-17T02:08:08Zhdl_2115_20044hdl_2115_124Involvement of heat-shock protein 90 in the interleukin-6-mediated signaling pathway through STAT3.Sato, NorikoYamamoto, TetsuyaSekine, YuichiYumioka, TaroJunicho, AkiraFuse, HidekiMatsuda, TadashiIL-6Heat-shock protein 90Signal transducer and activator of transcriptionGeldanamycin499.3Interleukin-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.ElsevierJournal Articleapplication/pdfhttp://hdl.handle.net/2115/28121https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/28121/1/BBRC300-4.pdf0006-291X1090-2104Biochemical and Biophysical Research Communications30048478522003-01-24enginfo:pmid/12559950info:doi/10.1016/S0006-291X(02)02941-8author