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PLoS One. 2011;6(12):e28998. doi: 10.1371/journal.pone.0028998. Epub 2011 Dec 20.

APC/C(Cdh1)-mediated degradation of the F-box protein NIPA is regulated by its association with Skp1.

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  • 1Department of Internal Medicine ΙΙΙ, Technical University of Munich, Munich, Germany.


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.

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