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1. 发明申请

US20130131153A1 CULLIN 5 AS A REGULATOR OF HSP90 CLIENTS: A NEW TARGET FOR DRUG DEVELOPMENT 审中-公开
标题翻译： CULLIN 5作为HSP90客户的监管者：药物开发的新目标
公开(公告)号：US20130131153A1
公开(公告)日：2013-05-23
申请号：US13510093
申请日：2010-11-16
申请人： Xiao-Fang Yu , Elana S. Ehrlich , Rongzhen Xu
发明人： Xiao-Fang Yu , Elana S. Ehrlich , Rongzhen Xu
IPC分类号： G01N33/573 , C12Q1/68
CPC分类号： G01N33/573 , C12Q1/68 , G01N33/5011 , G01N2333/9015
摘要： Cullin5 (Cul5) E3 ubiquitin ligase is shown to be linked with the heat shock protein 90 (Hsp90) chaperone complex. Hsp90 participates in the folding of its client proteins into their functional conformation. Many Hsp90 clients have been reported to be aberrantly expressed in a number of cancers. Cul5 is shown to interact with members of the Hsp90 chaperone complex as well as the Hsp90 client, ErbB2, Cul5 is recruited to the site of ErbB2 at the plasma membrane and subsequent induction of polyubiquitination and proteasomal degradation. Cul5 is also involved in the regulation of another Hsp90 client, Hif-1α Cul5 degradation of ErbB2 occurs independently of ElonginB-ElonginC function. The involvement of Cul5 in Hsp90 client regulation has implications in the effectiveness of Hsp90 targeted chemotherapy, which is currently undergoing clinical trials. The link between Cul5 and Hsp90 client regulation may represent an avenue for cancer drug development.
摘要翻译： Cullin5（Cul5）E3泛素连接酶显示与热休克蛋白90（Hsp90）伴侣复合物连接。 Hsp90参与将其客户蛋白质折叠成其功能构象。据报道，许多Hsp90客户在许多癌症中异常表达。 Cul5显示与Hsp90伴侣复合物以及Hsp90客户端的成员相互作用，ErbB2，Cul5被引入到质膜上的ErbB2位点，随后诱导多泛素化和蛋白酶体降解。 Cul5也参与另一个Hsp90客户端的调控，Hif-1al Cul5 ErbB2的降解独立于ElonginB-ElonginC功能发生。 Cul5参与Hsp90客户监管对Hsp90靶向化疗的有效性有影响，目前正在进行临床试验。 Cul5和Hsp90客户监管之间的联系可能代表了癌症药物开发的途径。

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