Abstract
Aurora B activation is triggered at the mitotic entry and required for proper microtubule-kinetochore attachment at mitotic phase. Therefore, Aurora B should be in inactive form in interphase to prevent aberrant cell cycle progression. However, it is unclear how the inactivation of Aurora B is sustained during interphase. In this study, we find that IK depletion-induced mitotic arrest leads to G2 arrest by Aurora B inhibition, indicating that IK depletion enhances Aurora B activation before mitotic entry. IK binds to Aurora B, and colocalizes on the nuclear foci during interphase. Our data further show that IK inhibits Aurora B activation through recruiting PP2A into IK and Aurora B complex. It is thus believed that IK, as a scaffold protein, guides PP2A into Aurora B to suppress its activity in interphase until mitotic entry.
Keywords:
Aurora B; Cell cycle; IK; Interphase; Mitosis; PP2A; Protein RED.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aurora Kinase B / antagonists & inhibitors
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Aurora Kinase B / metabolism*
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Benzamides / pharmacology
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Cytokines / antagonists & inhibitors
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Cytokines / genetics
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Cytokines / metabolism*
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Enzyme Activation / drug effects
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G2 Phase Cell Cycle Checkpoints / drug effects
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HEK293 Cells
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HeLa Cells
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Humans
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Interphase
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M Phase Cell Cycle Checkpoints
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Phosphorylation / drug effects
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Protein Binding
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Protein Kinase Inhibitors / pharmacology
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Protein Phosphatase 2 / metabolism*
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Quinazolines / pharmacology
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RNA Interference
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RNA, Small Interfering / metabolism
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Recombinant Proteins / isolation & purification
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Tubulin / metabolism
Substances
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4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline
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Benzamides
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Cytokines
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IK protein, human
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Protein Kinase Inhibitors
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Quinazolines
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RNA, Small Interfering
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Recombinant Proteins
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Tubulin
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AURKB protein, human
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Aurora Kinase B
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Protein Phosphatase 2