Imai Jun, Maruya Mikako, Yashiroda Hideki, Yahara Ichiro, Tanaka Keiji
Department of Molecular Oncology and Department of Cell Biology, Tokyo Metropolitan Institute of Medical Science, Honkomagome 3-18-22, Bunkyo-ku, Tokyo 113-8613, CREST, Japan.
EMBO J. 2003 Jul 15;22(14):3557-67. doi: 10.1093/emboj/cdg349.
Hsp90 has a diverse array of cellular roles including protein folding, stress response and signal transduction. Herein we report a novel function for Hsp90 in the ATP-dependent assembly of the 26S proteasome. Functional loss of Hsp90 using a temperature-sensitive mutant in yeast caused dissociation of the 26S proteasome. Conversely, these dissociated constituents reassembled in Hsp90-dependent fashion both in vivo and in vitro; the process required ATP-hydrolysis and was suppressed by the Hsp90 inhibitor geldanamycin. We also found genetic interactions between Hsp90 and several proteasomal Rpn (Regulatory particle non-ATPase subunit) genes, emphasizing the importance of Hsp90 to the integrity of the 26S proteasome. Our results indicate that Hsp90 interacts with the 26S proteasome and plays a principal role in the assembly and maintenance of the 26S proteasome.
热休克蛋白90（Hsp90）在细胞中具有多种作用，包括蛋白质折叠、应激反应和信号转导。在此，我们报道了Hsp90在26S蛋白酶体的ATP依赖性组装中的新功能。利用酵母中的温度敏感突变体使Hsp90功能丧失，导致26S蛋白酶体解离。相反，这些解离的成分在体内和体外都以依赖Hsp90的方式重新组装；该过程需要ATP水解，并且被Hsp90抑制剂格尔德霉素抑制。我们还发现Hsp90与几个蛋白酶体Rpn（调节颗粒非ATP酶亚基）基因之间存在遗传相互作用，强调了Hsp90对26S蛋白酶体完整性的重要性。我们的结果表明，Hsp90与26S蛋白酶体相互作用，并在26S蛋白酶体的组装和维持中起主要作用。
