Actin is the primary cellular receptor of bistramide A.
Basic Information
ID: ALA1221165
Journal: Nat Chem Biol
Title: Actin is the primary cellular receptor of bistramide A.
Authors: Statsuk AV, Bai R, Baryza JL, Verma VA, Hamel E, Wender PA, Kozmin SA.
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) delta, leading to the view that PKCdelta is the principal mediator of antiproliferative activity of this natural product. Contrary to this observation, we established that bistramide A binds PKCdelta with low affinity, does not activate this kinase in vitro and does not translocate GFP-PKCdelta. 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 synthetic9 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.
CiteXplore: 16372404
DOI: 10.1038/nchembio748
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