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

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....

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Bibliographic Details
Published in:Molecular cancer research 2007-09, Vol.5 (9), p.933-942
Main Authors: Amiri, Anahita, Noei, Farahnaz, Feroz, Tahir, Lee, Jonathan M
Format: Article
Language:English
Subjects:
actin
Actins - drug effects
Actins - physiology
Adenocarcinoma - enzymology
Adenocarcinoma - pathology
Antibiotics, Antineoplastic - pharmacology
Benzoquinones - pharmacology
Cell Line, Tumor
Cell motility and migration
Cell Movement
Control of cell cycle progression
Enzyme Activation - drug effects
Enzyme Inhibitors - pharmacology
Female
Geldanamycin
GTPase-Activating Proteins - drug effects
GTPase-Activating Proteins - metabolism
HeLa Cells
Humans
Intracellular Signaling Peptides and Proteins - metabolism
Lactams, Macrocyclic - pharmacology
Neoplasm Invasiveness
Protein-Serine-Threonine Kinases - metabolism
rho GTP-Binding Proteins - metabolism
rho-Associated Kinases
Uterine Cervical Neoplasms - enzymology
Uterine Cervical Neoplasms - pathology
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Summary: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 stress fiber formation in human tumor cell lines. Inactivation of Rho prevents geldanamycin-induced 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. (Mol Cancer Res 2007;5(9):933–42)
ISSN:1541-7786
1557-3125
DOI:10.1158/1541-7786.MCR-06-0362