Geldanamycin Anisimycins Activate Rho and Stimulate Rho- and ROCK-Dependent Actin Stress Fiber Formation

A. Amiri, F. Noei, T. Feroz, J. M. Lee
2007 Molecular Cancer Research  
Heat shock protein 90 (Hsp90) is a member of the heat shock family of molecular chaperones that regulate protein conformation and activity. Hsp90 regulates multiple cell signaling pathways by controlling the abundance and activity of several important protein kinases and cell cycle -related proteins. In this report, we show that inhibition of Hsp90 by geldanamycin or its derivative, 17-allylamino-17-desmethoxygeldamycin, leads to activation of the Rho GTPase and a dramatic increase in actin
more » ... ss fiber formation in human tumor cell lines. Inactivation of Rho prevents geldanamycininduced actin reorganization. Hsp90 inactivation does not alter the appearance of filopodia or lamellipodia and tubulin architecture is not visibly perturbed. Our observations suggest that Hsp90 has an important and specific role in regulating Rho activity and Rho-dependent actin cytoskeleton remodeling.
doi:10.1158/1541-7786.mcr-06-0362 pmid:17855662 fatcat:ifqy55kaurfj3hriwxfpoy46iy