Abstract
Microtubule interfering agents (MIAs) are anti-tumor drugs that inhibit microtubule dynamics, while kinesin spindle protein (KSP) inhibitors are substances that block the formation of the bipolar spindle during mitosis. All these compounds cause G2/M arrest and cell death. Using 2D-PAGE followed by Nano-LC-ESI-Q-ToF analysis, we found that MIAs such as vincristine (Oncovin) or paclitaxel (Taxol) and KSP inhibitors such as S-tritil-l-cysteine induce the phosphorylation of the nuclear protein p54(nrb) in HeLa cells. Furthermore, we demonstrate that cisplatin (Platinol), an anti-tumor drug that does not cause M arrest, does not induce this modification. We show that the G2/M arrest induced by MIAs is required for p54(nrb) phosphorylation. Finally, we demonstrate that CDK activity is required for MIA-induced phosphorylation of p54(nrb).
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents, Phytogenic / pharmacology*
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Cell Line
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Cisplatin / pharmacology
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Cysteine / analogs & derivatives
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Cysteine / pharmacology
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DNA-Binding Proteins
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Electrophoresis, Gel, Two-Dimensional
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G2 Phase / drug effects
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G2 Phase / physiology*
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Humans
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Kinesins / antagonists & inhibitors
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Kinesins / metabolism*
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Microtubules
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Mitosis / physiology*
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Mitosis Modulators / pharmacology
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Nuclear Matrix-Associated Proteins / metabolism*
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Octamer Transcription Factors / metabolism*
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Paclitaxel / pharmacology
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Phosphorylation
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RNA-Binding Proteins / metabolism*
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Tandem Mass Spectrometry
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Tubulin Modulators / pharmacology*
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Vincristine / pharmacology
Substances
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Antineoplastic Agents, Phytogenic
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DNA-Binding Proteins
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KIF11 protein, human
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Mitosis Modulators
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NONO protein, human
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Nuclear Matrix-Associated Proteins
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Octamer Transcription Factors
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RNA-Binding Proteins
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Tubulin Modulators
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3-tritylthio-L-alanine
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Vincristine
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Kinesins
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Cysteine
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Paclitaxel
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Cisplatin