Actin is the primary cellular receptor of bistramide a

Alexander V. Statsuk, Ruoli Bai, Jeremy L. Baryza, Vishal A. Verma, Ernest Hamel, Paul A. Wender, Sergey A. Kozmin*

*Corresponding author for this work

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Bistramide A (1) is a marine natural product with broad, potent antiproliferative effects. Bistramide A has been reported to selectively activate protein kinase C (PKC) δ, leading to the view that PKCδ is the principal mediator of antiproliferative activity of this natural product. Contrary to this observation, we established that bistramide A binds PKCδ with low affinity, does not activate this kinase in vitro and does not translocate GFP-PKCδ. Furthermore, we identified actin as the cellular receptor of bistramide A. We report that bistramide A disrupts the actin cytoskeleton, inhibits actin polymerization, depolymerizes filamentous F-actin in vitro and binds directly to monomeric G-actin in a 1:1 ratio with a Kd of 7 nM. We also constructed a fully synthetic bistramide A–based affinity matrix and isolated actin as a specific bistramide A–binding protein. This activity provides a molecular explanation for the potent antiproliferative effects of bistramide A, identifying it as a new biochemical tool for studies of the actin cytoskeleton and as a potential lead for development of a new class of antitumor agents.

Original languageEnglish (US)
Pages (from-to)383-388
Number of pages6
JournalNature Chemical Biology
Volume1
Issue number7
DOIs
StatePublished - Jan 1 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Statsuk, A. V., Bai, R., Baryza, J. L., Verma, V. A., Hamel, E., Wender, P. A., & Kozmin, S. A. (2005). Actin is the primary cellular receptor of bistramide a. Nature Chemical Biology, 1(7), 383-388. https://doi.org/10.1038/nchembio748