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Synthetic Triterpenoids Target the Arp2/3 Complex and Inhibit Branched Actin Polymerization*
- Source :
- Physiology and Pharmacology Publications
- Publication Year :
- 2010
- Publisher :
- American Society for Biochemistry and Molecular Biology, 2010.
-
Abstract
- Synthetic triterpenoids are anti-tumor agents that affect numerous cellular functions including apoptosis and growth inhibition. Here, we used mass spectrometric and protein array approaches and uncovered that triterpenoids associate with proteins of the actin cytoskeleton, including actin-related protein 3 (Arp3). Arp3, a subunit of the Arp2/3 complex, is involved in branched actin polymerization and the formation of lamellipodia. 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO)-Im and CDDO-Me were observed to 1) inhibit the localization of Arp3 and actin at the leading edge of cells, 2) abrogate cell polarity, and 3) inhibit Arp2/3-dependent branched actin polymerization. We confirmed our drug effects with siRNA targeting of Arp3 and observed a decrease in Rat2 cell migration. Taken together, our data suggest that synthetic triterpenoids target Arp3 and branched actin polymerization to inhibit cell migration.
- Subjects :
- Models, Molecular
Medical Physiology
Arp2/3 complex
Cell Migration
macromolecular substances
Biochemistry
Mass Spectrometry
Actin-Related Protein 2-3 Complex
Cell Movement
Animals
Humans
Actin-binding protein
Cdc42
Oleanolic Acid
Cytoskeleton
Protein Structure, Quaternary
Molecular Biology
Actin
Biochemistry, Biophysics, and Structural Biology
biology
Imidazoles
Actin remodeling
Cell Polarity
Biological Transport
Cell Biology
Actin cytoskeleton
Pharmacy and Pharmaceutical Sciences
Actins
Triterpenes
Cell biology
Rats
biology.protein
Lamellipodium
Protein Multimerization
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Physiology and Pharmacology Publications
- Accession number :
- edsair.doi.dedup.....f7760fa94d55ffc7a1280e2331d41e22