Cited by 61Cellular Mechanics and InteractionsMicrotubule and mitosis dynamicsProtein Kinase Regulation and GTPase Signaling

The natural product cucurbitacin E inhibits depolymerization of actin filaments

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Sörensen, Pia M., Iacob, Roxana E., Fritzsche, Marco, Engen, John R., Brieher, William M., Charras, Guillaume, Eggert, Ulrike S.·2012·ACS Chemical Biology

Abstract

Although 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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Authors
Sörensen, P. M., Iacob, R. E., Fritzsche, M., Engen, J. R., Brieher, W. M., Charras, G., & Eggert, U. S.
Affiliations
  • Harvard University (US)
  • Northeastern University (US)
  • London Centre for Nanotechnology (GB)
  • University of Illinois Urbana-Champaign (US)
Corresponding author
Eggert, Ulrike S.
Venue
ACS Chemical Biology
Published
2012-07-09
Volume
7
Issue
9
Pages
1502-1508
ISSN
  • 1554-8929 (ISSN-L)
  • 1554-8937
OpenAlex
W2005677786
Cited by
61
References
34
Citations by year
2024: 4 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 2 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 2 · 2015: 11 · 2014: 7 · 2013: 4
FWCI
3.33
Type
journal article
Language
en
Open access
Locations
  • ACS Chemical Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
National Institute of General Medical Sciences (R01GM082834, R01GM086507)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
cucurbitacin E, actin depolymerization, actin filament stabilization, jasplakinolide, F-actin binding, actin dynamics, plant natural products, live-cell imaging, cytokinesis, actin-based motility
MeSH terms
Actins, Animals, Biological Products, HeLa Cells, Humans, Actin Cytoskeleton, Rabbits, Triterpenes, Cucurbitaceae, Depsipeptides, Polymerization

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