Abstract
Wnt signaling plays critical roles in cell proliferation and carcinogenesis. In addition, numerous recent studies have shown that various Wnt signaling components are involved in mitosis and chromosomal instability. However, the role of Axin, a negative regulator of Wnt signaling, in mitosis has remained unclear. Using monoclonal antibodies against Axin, we found that Axin localizes to the centrosome and along mitotic spindles. This localization was suppressed by siRNA specific for Aurora A kinase and by Aurora kinase inhibitor. Interestingly, Axin over-expression altered the subcellular distribution of Plk1 and of phosphorylated glycogen synthase kinase (GSK3beta) without producing any notable changes in cellular phenotype. In the presence of Aurora kinase inhibitor, Axin over-expression induced the formation of cleavage furrow-like structures and of prominent astral microtubules lacking midbody formation in a subset of cells. Our results suggest that Axin modulates distribution of Axin-associated proteins such as Plk1 and GSK3beta in an expression level-dependent manner and these interactions affect the mitotic process, including cytokinesis under certain conditions, such as in the presence of Aurora kinase inhibitor.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / metabolism
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Aurora Kinase A
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Aurora Kinases
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Axin Protein
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cell Line
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Centrosome / metabolism*
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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Enzyme Inhibitors / metabolism
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Glycogen Synthase Kinase 3 / genetics
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Humans
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Mice
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Mice, Knockout
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Mitosis / physiology*
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Polo-Like Kinase 1
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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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, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Spindle Apparatus / metabolism*
Substances
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AXIN2 protein, human
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Antibodies, Monoclonal
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Axin Protein
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Cell Cycle Proteins
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Cytoskeletal Proteins
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Enzyme Inhibitors
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Protein Isoforms
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Proto-Oncogene Proteins
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RNA, Small Interfering
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Repressor Proteins
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Aurka protein, mouse
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Aurora Kinase A
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Aurora Kinases
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GSK3B protein, human
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, mouse
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Protein Serine-Threonine Kinases
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Glycogen Synthase Kinase 3