Abstract
Hsp90 proteins constitute one of the most conserved Hsp families. Many of the identified Hsp90 substrate proteins fall into two classes: transcription factors and signaling kinases. Hsp90 is an emerging therapeutic target for the treatment of cancer since those signaling proteins are associated with cancer cell survival and proliferation. Several small-molecule inhibitors of Hsp90 have shown potent antitumor activity, and are currently in clinical investigation.
The purpose of the present study is to find novel small-molecule compounds that regulate the Hsp90 function. We purified the full-length and various truncated Hsp90 (HtpG) of the cyanobacterium Synechococcus elongatus PCC 7942. We performed chemical array analysis to identify compounds that interact with HtpG. We found that lipopeptide antibiotics bind to HtpG. Next, we investigated effect of these compounds on ATPase activity and chaperone holdase (anti-aggregation) activity of HtpG. They showed no effect on the ATPase activity, but inhibited the holdase activity greatly.
