Journal
CHEMISTRY & BIOLOGY
Volume 18, Issue 1, Pages 131-139Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2010.10.017
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Funding
- MEXT(JSPS) KAKENHI [21310140, 21870016]
- Uehara Memorial Foundation
- Naito Foundation
- National Institutes of Health [CA109277]
- Inoue Foundation of Science
- Grants-in-Aid for Scientific Research [21310140, 21870016, 23510277] Funding Source: KAKEN
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Aurilide is a potent cytotoxic marine natural product that induces apoptosis in cultured human cells at the picomolar to nanomolar range; however, its mechanism of action has been unknown. Results of the present study showed that aurilide selectively binds to prohibitin 1 (PHB1) in the mitochondria, activating the proteolytic processing of optic atrophy 1 (OPA1) and resulting in mitochondria-induced apoptosis. The mechanism of aurilide cytotoxicity suggests that PHB1 is an apoptosis-regulating protein amenable to modulation by small molecules. Aurilide may serve as a small-molecule tool for studies of mitochondria-induced apoptosis.
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