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 language | English (US) |
|---|---|
| Pages (from-to) | 33-38 |
| Number of pages | 6 |
| Journal | Nature Chemical Biology |
| Volume | 2 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2006 |
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ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Actin microfilament aggregation induced by withaferin A is mediated by annexin II
AU - Falsey, Ryan R.
AU - Marron, Marilyn T.
AU - Gunaherath, G. M Kamal B
AU - Shirahatti, Nikhil
AU - Mahadevan, Daruka
AU - Gunatilaka, Leslie
AU - Whitesell, Luke
PY - 2006/1
Y1 - 2006/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33645235842&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645235842&partnerID=8YFLogxK
U2 - 10.1038/nchembio755
DO - 10.1038/nchembio755
M3 - Article
C2 - 16408090
AN - SCOPUS:33645235842
VL - 2
SP - 33
EP - 38
JO - Nature Chemical Biology
JF - Nature Chemical Biology
SN - 1552-4450
IS - 1
ER -