Abstract
NIPA (Nuclear Interaction Partner of Alk kinase) is an F-box like protein that targets nuclear Cyclin B1 for degradation. Integrity and therefore activity of the SCF(NIPA) E3 ligase is regulated by cell-cycle-dependent phosphorylation of NIPA, restricting substrate ubiquitination to interphase. Here we show that phosphorylated NIPA is degraded in late mitosis in an APC/C(Cdh1)-dependent manner. Binding of the unphosphorylated form of NIPA to Skp1 interferes with binding to the APC/C-adaptor protein Cdh1 and therefore protects unphosphorylated NIPA from degradation in interphase. Our data thus define a novel mode of regulating APC/C-mediated ubiquitination.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / chemistry
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Adaptor Proteins, Signal Transducing / metabolism*
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Amino Acid Sequence
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Anaphase-Promoting Complex-Cyclosome
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Animals
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Cell Cycle Proteins / chemistry
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Cell Cycle Proteins / metabolism*
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F-Box Proteins / chemistry
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F-Box Proteins / metabolism*
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HEK293 Cells
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HeLa Cells
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Humans
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Mice
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Mitosis
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Molecular Sequence Data
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NIH 3T3 Cells
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Nuclear Proteins / chemistry
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Nuclear Proteins / metabolism*
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Phosphorylation
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Protein Binding
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Protein Structure, Tertiary
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Proteolysis*
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S-Phase Kinase-Associated Proteins / metabolism*
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Ubiquitin-Protein Ligase Complexes / metabolism*
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Ubiquitination
Substances
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Adaptor Proteins, Signal Transducing
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Cell Cycle Proteins
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F-Box Proteins
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Nuclear Proteins
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S-Phase Kinase-Associated Proteins
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ZC3HC1 protein, human
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Ubiquitin-Protein Ligase Complexes
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Anaphase-Promoting Complex-Cyclosome