期刊
CHEMISTRY & BIOLOGY
卷 16, 期 11, 页码 1158-1168出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2009.10.006
关键词
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资金
- National Institutes of Health [RO1GM079265, 5DP1OD003354]
- American Cancer Society [RSG-04-017-CDD]
- Burroughs Wellcome Career
Formins stimulate actin filament assembly for fundamental cellular processes including division, adhesion, establishing polarity, and motility. A formin inhibitor would be useful because most cells express multiple formins whose functions are not known and because metastatic tumor formation depends on the deregulation of formin-dependent processes. We identified a general small molecule inhibitor of formin homology 2 domains (SMIFH2) by screening compounds for the ability to prevent formin-mediated actin assembly in vitro. SMIFH2 targets formins from evolutionarily diverse organisms including yeast, nematode worm, and mice, with a half-maximal inhibitor concentration of similar to 5 to 15 mu M. SMIFH2 prevents both formin nucleation and processive barbed end elongation and decreases formin's affinity for the barbed end. Furthermore, low micromolar concentrations of SMIFH2 disrupt formin-dependent, but not Arp2/3 complex-dependent, actin cytoskeletal structures in fission yeast and mammalian NIH 3T3 fibroblasts.
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