1 research outputs found
Cruentaren A Binds F<sub>1</sub>F<sub>0</sub> ATP Synthase To Modulate the Hsp90 Protein Folding Machinery
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 F<sub>1</sub>F<sub>0</sub> ATP synthase by cruentaren A was shown to disrupt
the Hsp90-F<sub>1</sub>F<sub>0</sub> ATP synthase interaction and
result in client protein degradation without induction of the HSR