Unknown

Dataset Information

0

Cruentaren A binds F1F0 ATP synthase to modulate the Hsp90 protein folding machinery.


ABSTRACT: The molecular chaperone Hsp90 requires the assistance of immunophilins, co-chaperones, and partner proteins for the conformational maturation of client proteins. Hsp90 inhibition represents a promising anticancer strategy due to the dependence of numerous oncogenic signaling pathways upon Hsp90 function. Historically, small molecules have been designed to inhibit ATPase activity at the Hsp90 N-terminus; however, these molecules also induce the pro-survival heat shock response (HSR). Therefore, inhibitors that exhibit alternative mechanisms of action that do not elicit the HSR are actively sought. Small molecules that disrupt Hsp90-co-chaperone interactions can destabilize the Hsp90 complex without induction of the HSR, which leads to inhibition of cell proliferation. In this article, selective inhibition of F1F0 ATP synthase by cruentaren A was shown to disrupt the Hsp90-F1F0 ATP synthase interaction and result in client protein degradation without induction of the HSR.

SUBMITTER: Hall JA 

PROVIDER: S-EPMC4090037 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC2978574 | biostudies-literature
| S-EPMC4772093 | biostudies-literature
| S-EPMC3060467 | biostudies-literature
| S-EPMC2172039 | biostudies-literature
| S-EPMC3788808 | biostudies-literature
| S-EPMC6335059 | biostudies-literature
| S-EPMC2577739 | biostudies-literature
| S-EPMC2713559 | biostudies-literature
| S-EPMC7526845 | biostudies-literature
| S-EPMC3837435 | biostudies-literature