The Natural Product Cucurbitacin E Inhibits Depolymerization of Actin Filaments
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Iacob, Roxana, E.
Engen, John R.
Brieher, William M.
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CitationSorensen, Pia M., Roxana E. Iacob, Marco Fritzsche, John R. Engen, William M. Brieher, Guillaume Charras, and Ulrike S. Eggert. 2012. The Natural Product Cucurbitacin E Inhibits Depolymerization of Actin Filaments. ACS Chemical Biology 7, no. 9: 1502-508.
AbstractAlthough small molecule actin modulators have been widely used as research tools, only one cell-permeable small molecule inhibitor of actin depolymerization (jasplakinolide) is commercially available. We report that the natural product cucurbitacin E inhibits actin depolymerization and show that its mechanism of action is different from jasplakinolide. In assays using pure fluorescently labeled actin, cucurbitacin E specifically affects depolymerization without affecting polymerization. It inhibits actin depolymerization at substoichiometric concentrations up to 1:6 cucurbitacin E:actin. Cucurbitacin E specifically binds to filamentous actin (F-actin) forming a covalent bond at residue Cys257, but not to monomeric actin (G-actin). On the basis of its compatibility with phalloidin staining, we show that cucurbitacin E occupies a different binding site on actin filaments. Using loss of fluorescence after localized photoactivation, we found that cucurbitacin E inhibits actin depolymerization in live cells. Cucurbitacin E is a widely available plant-derived natural product, making it a useful tool to study actin dynamics in cells and actin-based processes such as cytokinesis.
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