Actin microfilament aggregation induced by withaferin A is mediated by annexin II

Ryan R. Falsey, Marilyn T. Marron, G. M Kamal B Gunaherath, Nikhil Shirahatti, Daruka Mahadevan, Leslie Gunatilaka, Luke Whitesell

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

The actin cytoskeleton supports diverse cellular processes such as endocytosis, oriented growth, adhesion and migration1. The dynamic nature of the cytoskeleton, however, has made it difficult to define the roles of the many accessory molecules that modulate actin organization, especially the multifunctional adapter protein annexin II (refs. 2,3). We now report that the compound withaferin A (1) can alter cytoskeletal architecture in a previously unknown manner by covalently binding annexin II and stimulating its basal F-actin cross-linking activity. Drug-mediated disruption of F-actin organization is dependent on annexin II expression by cells and markedly limits their migratory and invasive capabilities at subcytotoxic concentrations. Given the extensive ethnobotanical history of withaferin-containing plant preparations in the treatment of cancer and inflammatory and neurological disorders, we suggest that annexin II represents a feasible, previously unexploited target for therapeutic intervention by small-molecule drugs4.

Original languageEnglish (US)
Pages (from-to)33-38
Number of pages6
JournalNature Chemical Biology
Volume2
Issue number1
DOIs
StatePublished - Jan 2006

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Annexin A2
Actin Cytoskeleton
Actins
Plant Preparations
Endocytosis
Nervous System Diseases
Cytoskeleton
History
withaferin A
Growth
Pharmaceutical Preparations
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Falsey, R. R., Marron, M. T., Gunaherath, G. M. K. B., Shirahatti, N., Mahadevan, D., Gunatilaka, L., & Whitesell, L. (2006). Actin microfilament aggregation induced by withaferin A is mediated by annexin II. Nature Chemical Biology, 2(1), 33-38. https://doi.org/10.1038/nchembio755

Actin microfilament aggregation induced by withaferin A is mediated by annexin II. / Falsey, Ryan R.; Marron, Marilyn T.; Gunaherath, G. M Kamal B; Shirahatti, Nikhil; Mahadevan, Daruka; Gunatilaka, Leslie; Whitesell, Luke.

In: Nature Chemical Biology, Vol. 2, No. 1, 01.2006, p. 33-38.

Research output: Contribution to journalArticle

Falsey, RR, Marron, MT, Gunaherath, GMKB, Shirahatti, N, Mahadevan, D, Gunatilaka, L & Whitesell, L 2006, 'Actin microfilament aggregation induced by withaferin A is mediated by annexin II', Nature Chemical Biology, vol. 2, no. 1, pp. 33-38. https://doi.org/10.1038/nchembio755
Falsey, Ryan R. ; Marron, Marilyn T. ; Gunaherath, G. M Kamal B ; Shirahatti, Nikhil ; Mahadevan, Daruka ; Gunatilaka, Leslie ; Whitesell, Luke. / Actin microfilament aggregation induced by withaferin A is mediated by annexin II. In: Nature Chemical Biology. 2006 ; Vol. 2, No. 1. pp. 33-38.
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