Molecular Entomology Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Biochem Biophys Res Commun. 2011 Apr 22;407(4):720-4. doi: 10.1016/j.bbrc.2011.03.088. Epub 2011 Mar 31.
Previously, we found that treatment of cells with the Hsp90 inhibitor geldanamycin (GA) leads to a substantial reduction in the number of processing bodies (P-bodies), and also alters the size and subcellular localization of stress granules. These findings imply that the chaperone activity of Hsp90 is involved in the formation of P-bodies and stress granules. To verify these observations, we examined whether another Hsp90 inhibitor radicicol (RA) affected P-bodies and stress granules. Treatment with RA reduced the level of the Hsp90 client protein Argonaute 2 and the number of P-bodies. Although stress granules still assembled in RA-treated cells upon heat shock, they were smaller and more dispersed in the cytoplasm than those in untreated cells. Furthermore eIF4E and eIF4E-transporter were dissociated selectively from stress granules in RA-treated cells. These observations were comparable to those obtained upon treatment with GA in our previous work. Thus, we conclude that abrogation of the chaperone activity of Hsp90 affects P-body formation and the integrity of stress granules.
先前，我们发现用热休克蛋白 90（Hsp90）抑制剂格尔德霉素（GA）处理细胞会导致大量的处理体（P 体）减少，同时改变应激颗粒的大小和亚细胞定位。这些发现表明 Hsp90 的伴侣活性参与了 P 体和应激颗粒的形成。为了验证这些观察结果，我们检查了另一种 Hsp90 抑制剂雷地昔醇（RA）是否影响 P 体和应激颗粒。用 RA 处理会降低 Hsp90 客户蛋白 Argonaute 2 的水平和 P 体的数量。尽管在热休克时应激颗粒仍在 RA 处理的细胞中组装，但它们比未处理的细胞更小且在细胞质中更分散。此外，eIF4E 和 eIF4E 转运蛋白在 RA 处理的细胞中选择性地从应激颗粒解离。这些观察结果与我们之前的工作中用 GA 处理时获得的结果相当。因此，我们得出结论，Hsp90 的伴侣活性的阻断会影响 P 体的形成和应激颗粒的完整性。
