APC/CCdh1-Mediated Degradation of the F-Box Protein NIPA Is Regulated by Its Association with Skp1

NIPA (Nuclear Interaction Partner of Alk kinase) is an F-box like proteinthat targets nuclear Cyclin B1 for degradation. Integrity and therefore activityof the SCFNIPA E3 ligase is regulated by cell-cycle-dependent phosphorylationof NIPA, restricting substrate ubiquitination to interphase. Here we showthat phosphorylated NIPA is degraded in late mitosis in an APC/CCdh1-dependentmanner. Binding of the unphosphorylated form of NIPA to Skp1 interferes withbinding to the APC/C-adaptor protein Cdh1 and therefore protects unphosphorylatedNIPA from degradation in interphase. Our data thus define a novel mode ofregulating APC/C-mediated ubiquitination.