The natural product cucurbitacin E inhibits depolymerization of actin filaments
Open accessAbstract
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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Cucurbitacin E and I are less likely to be protective compounds since they appear to induce cell death in various cancers.
“Curbitacini E & I, are less likely to be protective compounds since they apear to induce cell death in various cancers29,30”
From Bacopa monnieri (L.) wettst. Extract protects against glutamate toxicity and increases the longevity of Caenorhabditis elegans (2020) · cites this paper as [29]
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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.
- ORCID
- Venue
- ACS Chemical Biology
- Publisher
- American Chemical Society (ACS)
- Published
- 2012-07-09
- Volume
- 7
- Issue
- 9
- Pages
- 1502-1508
- ISSN
- 1554-8929 (ISSN-L)
- 1554-8937
- PMC
- PMC3448819
- 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
- green
- europepmc.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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