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Science 10 April 1998: Vol. 280. no. 5361, pp. 292 - 295 DOI: 10.1126/science.280.5361.292
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Reports
A Marine Natural Product Inhibitor of Kinesin Motors
Roman Sakowicz,
Michael S. Berdelis,
Krishanu Ray,
Christine L. Blackburn,
Cordula Hopmann,
D. John Faulkner,
Lawrence S. B. Goldstein
*
Members of the kinesin superfamily of motor proteins are essential
for mitotic and meiotic spindle organization, chromosome segregation,
organelle and vesicle transport, and many other processes that require
microtubule-based transport. A compound, adociasulfate-2, was isolated
from a marine sponge, Haliclona (also known as
Adocia) species, that inhibited kinesin activity by
targeting its motor domain and mimicking the activity of the
microtubule. Thus, the kinesin-microtubule interaction site could be a
useful target for small molecule modulators, and adociasulfate-2 should
serve as an archetype for specific inhibitors of kinesin functions.
R. Sakowicz, M. S. Berdelis, K. Ray, L. S. B. Goldstein, Department of Pharmacology, Division of Cellular and
Molecular Medicine, Howard Hughes Medical Institute, University of
California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0683,
USA.
C. L. Blackburn, C. Hopmann, D. J. Faulkner, Scripps Institution
of Oceanography, University of California, San Diego, La Jolla, CA
92093-0212, USA.
*
To whom correspondence should be addressed. E-mail:
lgoldstein{at}ucsd.edu
Read the Full Text
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- Targeting the Kinesin Spindle Protein: Basic Principles and Clinical Implications.
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- Antitumor Activity of a Kinesin Inhibitor.
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- Myosin Va and microtubule-based motors are required for fast axonal retrograde transport of tetanus toxin in motor neurons.
- G. Lalli, S. Gschmeissner, and G. Schiavo (2003)
J. Cell Sci.
116, 4639-4650
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- Bidirectional Translocation of Neurofilaments along Microtubules Mediated in Part by Dynein/Dynactin.
- J. V. Shah, L. A. Flanagan, P. A. Janmey, and J.-F. Leterrier (2000)
Mol. Biol. Cell
11, 3495-3508
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- Allele-specific activators and inhibitors for kinesin.
- T. M. Kapoor and T. J. Mitchison (1999)
PNAS
96, 9106-9111
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