Centrosomal AKAP350 modulates the G1/S transition

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dc.citation.titleCellular Logistics
dc.citation.volume3
dc.creatorMattaloni, Stella M.
dc.creatorFerretti, Anabela Cecilia
dc.creatorTonucci, Facundo Mauro
dc.creatorFavre, Cristian
dc.creatorGoldenring, James R.
dc.creatorLarocca, María Cecilia
dc.date.accessioned2024-05-30T19:00:53Z
dc.date.available2024-05-30T19:00:53Z
dc.date.issued2013-10-10
dc.description.abstractAKAP350 (AKAP450/AKAP9/CG-NAP) is an A-kinase anchoring protein, which recruits multiple signaling proteins to the Golgi apparatus and the centrosomes. Several proteins recruited to the centrosomes by this scaffold participatein the regulation of the cell cycle. Previous studies indicated that AKAP350 participates in centrosome duplication. In the present study we specifically assessed the role of AKAP350 in the progression of the cell cycle. Our results showed that interference with AKAP350 expression inhibits G1/S transition, decreasing the initiation of both DNA synthesis and centrosome duplication. We identified an AKAP350 carboxyl-terminal domain (AKAP350CTD), which contained the centrosomal targeting domain of AKAP350 and induced the initiation of DNA synthesis. Nevertheless, AKAP350CTD expression did not induce centrosomal duplication. AKAP350CTD partially delocalized endogenous AKAP350 from the centrosomes, but increased the centrosomal levels of the cyclin-dependent kinase 2 (Cdk2). Accordingly, the expression of this AKAP350 domain increased the endogenous phosphorylation of nucleophosmin by Cdk2, which occurs at the G1 /S transition and is a marker of the centrosomal activity of the cyclin E-Cdk2 complex. Cdk2 recruitment to the centrosomes is a necessary event for the development of the G1/S transition. Altogether, our results indicate that AKAP350 facilitates the initiation of DNA synthesis by scaffolding Cdk2 to the centrosomes, and enabling its specific activity at this organelle. Although this mechanism could also be involved in AKAP350-dependent modulation of centrosomal duplication, it is not sufficient to account for this process.
dc.description.filFil: Mattaloni, Stella M. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Consejo de Investigaciones Científicas y Técnicas. Instituto de Fisiología Experimental (CONICET-IFISE); Argentina.
dc.description.filFil: Ferretti, Anabela Cecilia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Consejo de Investigaciones Científicas y Técnicas. Instituto de Fisiología Experimental (CONICET-IFISE); Argentina.
dc.description.filFil: Tonucci, Facundo Mauro. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Consejo de Investigaciones Científicas y Técnicas. Instituto de Fisiología Experimental (CONICET-IFISE); Argentina.
dc.description.filFil: Favre, Cristian. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Consejo de Investigaciones Científicas y Técnicas. Instituto de Fisiología Experimental (CONICET-IFISE); Argentina.
dc.description.filFil: Goldenring, James R. Vanderbilt-Ingram Cancer Center and the Nashville VA Medical Center. Vanderbilt University School of Medicine. Epithelial Biology Center. Departments of Surgery and Cell and Developmental Biology.; USA.
dc.description.filFil: Larocca, María Cecilia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Consejo de Investigaciones Científicas y Técnicas. Instituto de Fisiología Experimental (CONICET-IFISE); Argentina.
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas
dc.description.sponsorshipAgencia Nacional de Promoción Científica y Tecnológica (ANPCyT): PIP 0652, PICTs 01865, 2012-2198
dc.format.extent1-8
dc.identifier.issn2159-2799
dc.identifier.urihttps://hdl.handle.net/2133/27109
dc.language.isoen
dc.publisherLandes Bioscience
dc.relation.publisherversionhttps://www.tandfonline.com/doi/full/10.4161/cl.26331
dc.relation.publisherversionhttps://doi.org/10.4161/cl.26331
dc.rightsopenAccess
dc.rights.holderLandes Bioscience
dc.rights.holderUniversidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas
dc.rights.textAttribution-NonCommercial 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectAKAP350
dc.subjectAKAP450
dc.subjectCG-NAP
dc.subjectCdk2
dc.subjectCentrosome
dc.subjectG1/S transition
dc.titleCentrosomal AKAP350 modulates the G1/S transition
dc.typearticulo
dc.type.collectionarticulo
dc.type.versionpublishedVersion

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