title: Microtubule interfering agents and KSP inhibitors induce the phosphorylation of the nuclear protein p54(nrb), an event linked to G2/M arrest.
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).
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, 33071, Oviedo, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Casado
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Prado
authors.forename: Pedro
authors.initials: P
authors.lastname: Zuazua-Villar
authors.forename: Eva
authors.initials: E
authors.lastname: Del Valle
authors.forename: Noelia
authors.initials: N
authors.lastname: Artime
authors.forename: Lucía
authors.initials: L
authors.lastname: Cabal-Hierro
authors.forename: Patricia
authors.initials: P
authors.lastname: Rupérez
authors.forename: Alma L
authors.initials: AL
authors.lastname: Burlingame
authors.forename: Pedro S
authors.initials: PS
authors.lastname: Lazo
authors.forename: Sofía
authors.initials: S
authors.lastname: Ramos
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004268:DNA-Binding Proteins; D015180:Electrophoresis, Gel, Two-Dimensional; D016195:G2 Phase / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008870:Microtubules; D008938:Mitosis / Q000502:physiology*; D050258:Mitosis Modulators / Q000494:pharmacology; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D050810:Octamer Transcription Factors / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D050257:Tubulin Modulators / Q000494:pharmacology*; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; C470243:KIF11 protein, human; D050258:Mitosis Modulators; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D016601:RNA-Binding Proteins; D050257:Tubulin Modulators; C003724:3-tritylthio-L-alanine; D014750:Vincristine; D016547:Kinesins; D003545:Cysteine; D017239:Paclitaxel; D002945:Cisplatin