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APC/C(Cdh1)-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 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.

Pubmed ID: 22205987


  • Klitzing Cv
  • Huss R
  • Illert AL
  • Fröschl A
  • Wötzel S
  • Peschel C
  • Bassermann F
  • Duyster J


PloS one

Publication Data

December 29, 2011

Associated Grants


Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Cell Cycle Proteins
  • F-Box Proteins
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mice
  • Mitosis
  • Molecular Sequence Data
  • NIH 3T3 Cells
  • Nuclear Proteins
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Tertiary
  • Proteolysis
  • S-Phase Kinase-Associated Proteins
  • Ubiquitin-Protein Ligase Complexes
  • Ubiquitination