Cullen 5 As a Regulator of Hsp90 Clients: a New Target for Drug Development
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-1a 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.
YU XIAO-FANG [US]; EHRLICH ELANA S [US]; XU RONGZHEN [CN]
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