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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
1998-9-8
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pubmed:abstractText |
Cryptophycin-52 (LY355703) is a new synthetic member of the cryptophycin family of antimitotic antitumor agents that is currently undergoing clinical evaluation. At high concentrations (>/=10 times the IC50), cryptophycin-52 blocked HeLa cell proliferation at mitosis by depolymerizing spindle microtubules and disrupting chromosome organization. However, low concentrations of cryptophycin-52 inhibited cell proliferation at mitosis (IC50 = 11 pM) without significantly altering spindle microtubule mass or organization. Cryptophycin-52 appears to be the most potent suppressor of microtubule dynamics found thus far. It suppressed the dynamic instability behavior of individual microtubules in vitro (IC50 = 20 nM), reducing the rate and extent of shortening and growing without significantly reducing polymer mass or mean microtubule length. Using [3H]cryptophycin-52, we found that the compound bound to microtubule ends in vitro with high affinity (Kd, 47 nM, maximum of approximately 19.5 cryptophycin-52 molecules per microtubule). By analyzing the effects of cryptophycin-52 on dynamics in relation to its binding to microtubules, we determined that approximately 5-6 molecules of cryptophycin-52 bound to a microtubule were sufficient to decrease dynamicity by 50%. Cryptophycin-52 became concentrated in cells 730-fold, and the resulting intracellular cryptophycin-52 concentration was similar to that required to stabilize microtubule dynamics in vitro. The data suggest that cryptophycin-52 potently perturbs kinetic events at microtubule ends that are required for microtubule function during mitosis and that it acts by forming a reversible cryptophycin-52-tubulin stabilizing cap at microtubule ends.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-1506423,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-2009540,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-2379239,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-2391359,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-3170635,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-3713844,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-6504138,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-7027052,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-7632691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-7857932,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-7913408,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-8105478,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-8298190,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-8349735,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-8432733,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-8448138,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-8534917,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-8543019,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-8598048,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-8626409,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-8631019,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-8813133,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-8939919,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-8985015,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-9335554,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-9380674,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-9383460,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689077-942051
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
95
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9313-8
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:9689077-Antineoplastic Agents,
pubmed-meshheading:9689077-Biopolymers,
pubmed-meshheading:9689077-Cell Division,
pubmed-meshheading:9689077-Depsipeptides,
pubmed-meshheading:9689077-HeLa Cells,
pubmed-meshheading:9689077-Humans,
pubmed-meshheading:9689077-Kinetics,
pubmed-meshheading:9689077-Lactams,
pubmed-meshheading:9689077-Lactones,
pubmed-meshheading:9689077-Microtubules,
pubmed-meshheading:9689077-Peptides, Cyclic
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pubmed:year |
1998
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pubmed:articleTitle |
Antiproliferative mechanism of action of cryptophycin-52: kinetic stabilization of microtubule dynamics by high-affinity binding to microtubule ends.
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pubmed:affiliation |
Department of Molecular Cellular and Developmental Biology, University of California at Santa Barbara, Santa Barbara, CA 93106, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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