Amiri Anahita, Noei Farahnaz, Feroz Tahir, Lee Jonathan M
Department of Biochemistry, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
Mol Cancer Res. 2007 Sep;5(9):933-42. doi: 10.1158/1541-7786.MCR-06-0362.
Heat shock protein 90 (Hsp90) is a member of the heat shock family of molecular chaperones that regulate protein conformation and activity. Hsp90 regulates multiple cell signaling pathways by controlling the abundance and activity of several important protein kinases and cell cycle-related proteins. In this report, we show that inhibition of Hsp90 by geldanamycin or its derivative, 17-allylamino-17-desmethoxygeldamycin, leads to activation of the Rho GTPase and a dramatic increase in actin stress fiber formation in human tumor cell lines. Inactivation of Rho prevents geldanamycin-induced actin reorganization. Hsp90 inactivation does not alter the appearance of filopodia or lamellipodia and tubulin architecture is not visibly perturbed. Our observations suggest that Hsp90 has an important and specific role in regulating Rho activity and Rho-dependent actin cytoskeleton remodeling.
热休克蛋白90（Hsp90）是分子伴侣热休克家族的成员，可调节蛋白质的构象和活性。Hsp90通过控制几种重要蛋白激酶和细胞周期相关蛋白的丰度和活性来调节多种细胞信号通路。在本报告中，我们表明，格尔德霉素或其衍生物17-烯丙基氨基-17-去甲氧基格尔德霉素对Hsp90的抑制会导致人肿瘤细胞系中Rho GTP酶的激活以及肌动蛋白应力纤维形成的显著增加。Rho的失活可阻止格尔德霉素诱导的肌动蛋白重组。Hsp90失活不会改变丝状伪足或片状伪足的外观，微管结构也未受到明显干扰。我们的观察结果表明，Hsp90在调节Rho活性和Rho依赖性肌动蛋白细胞骨架重塑中具有重要且特定的作用。
