Letter abstract
Nature Chemical Biology 2, 33 - 38 (2005)
Published online: 11 December 2005 | doi:10.1038/nchembio755
Actin microfilament aggregation induced by withaferin A is mediated by annexin II
Ryan R Falsey1,2, Marilyn T Marron2, G M Kamal B Gunaherath3, Nikhil Shirahatti1, Daruka Mahadevan1, A A Leslie Gunatilaka1,3 & Luke Whitesell1,2
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.
- Cancer Biology Interdisciplinary Graduate Program University of Arizona Health Sciences Center, 1501 North Campbell Avenue, Tucson, Arizona 85724, USA.
- Steele Memorial Children's Research Center, University of Arizona Health Sciences Center, 1501 North Campbell Avenue, Tucson, Arizona 85724, USA.
- Southwest Center for Natural Products Research, University of Arizona, 250 East Valencia Road, Tucson, Arizona 85706, USA.
Correspondence to: Luke Whitesell1,2 e-mail: whitesell@wi.mit.edu
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