RGD Reference Report - Synthetic triterpenoids target the Arp2/3 complex and inhibit branched actin polymerization. - Rat Genome Database

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Synthetic triterpenoids target the Arp2/3 complex and inhibit branched actin polymerization.

Authors: To, C  Shilton, BH  Di Guglielmo, GM 
Citation: To C, etal., J Biol Chem. 2010 Sep 3;285(36):27944-57. doi: 10.1074/jbc.M110.103036. Epub 2010 Jun 21.
RGD ID: 11530051
Pubmed: PMID:20566646   (View Abstract at PubMed)
PMCID: PMC2934661   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M110.103036   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to triterpenoid  IEP 11530051 RGD 
positive regulation of fibroblast migration  IMP 11530051 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell leading edge  IDA 11530051 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
actin binding  IDA 11530051 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Actr3  (actin related protein 3)
Wasl  (WASP like actin nucleation promoting factor)


Additional Information