Abstract
Aurora-A and Plk1 are centrosomal kinases involved in centrosome maturation and spindle assembly. The microtubule-binding protein TPX2 interacts with, and activates, Aurora-A. Here we have used RNA interference-mediated inactivation to investigate whether Aurora-A, Plk1 and TPX2 act independently or are part of one signaling cascade in spindle formation in mammalian cells. We have identified both specific, and over- lapping, roles of each single regulator in centrosome maturation and spindle formation: (1) Aurora-A and TPX2 are required for centriole cohesion and spindle bipolarity; (2) TPX2, besides its known role in microtubule organization, is also involved in centrosome maturation; (3) finally, Plk1 controls the localization of Aurora-A to centrosomes, as well as TPX2 recruitment to microtubules. Based on these results therefore a hierarchical functional relation between Plk1 and the Aurora-A/TPX2 pathway emerges.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aurora Kinases
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Base Sequence
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Line, Tumor
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Humans
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism*
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Mitosis / physiology*
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Molecular Sequence Data
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Polo-Like Kinase 1
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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RNA Interference
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Signal Transduction
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Spindle Apparatus / metabolism*
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Spindle Apparatus / ultrastructure
Substances
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Cell Cycle Proteins
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Microtubule-Associated Proteins
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Neoplasm Proteins
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Nuclear Proteins
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Phosphoproteins
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Proto-Oncogene Proteins
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TPX2 protein, human
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Aurora Kinases
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Protein Serine-Threonine Kinases