Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase

Dev Cell. 2003 Jun;4(6):813-26. doi: 10.1016/s1534-5807(03)00153-9.


Progression through mitosis occurs because cyclin B/Cdc2 activation induces the anaphase promoting complex (APC) to cause cyclin B destruction and mitotic exit. To ensure that cyclin B/Cdc2 does not prematurely activate the APC in early mitosis, there must be a mechanism delaying APC activation. Emi1 is a protein capable of inhibiting the APC in S and G2. We show here that Emi1 is phosphorylated by Cdc2, and on a DSGxxS consensus site, is subsequently recognized by the SCF(betaTrCP/Slimb) ubiquitin ligase and destroyed, thus providing a delay for APC activation. Failure of betaTrCP-dependent Emi1 destruction stabilizes APC substrates and results in mitotic catastrophe including centrosome overduplication, potentially explaining mitotic deficiencies in Drosophila Slimb/betaTrCP mutants. We hypothesize that Emi1 destruction relieves a late prophase checkpoint for APC activation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Consensus Sequence
  • Cyclin A / metabolism
  • Cyclin B / metabolism
  • Drosophila Proteins
  • Enzyme Activation
  • F-Box Proteins
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism
  • Humans
  • Mitosis* / drug effects
  • Models, Biological
  • Mutation
  • Nocodazole / pharmacology
  • Oocytes / cytology
  • Oocytes / physiology
  • Peptide Synthases / metabolism*
  • Phosphorylation
  • SKP Cullin F-Box Protein Ligases
  • Swine
  • Time Factors
  • Xenopus
  • Xenopus Proteins*
  • beta-Transducin Repeat-Containing Proteins


  • BTRC protein, Xenopus
  • BTRC protein, human
  • Cell Cycle Proteins
  • CycB protein, Drosophila
  • Cyclin A
  • Cyclin B
  • Drosophila Proteins
  • F-Box Proteins
  • FBXO5 protein, Xenopus
  • FBXO5 protein, human
  • Xenopus Proteins
  • beta-Transducin Repeat-Containing Proteins
  • SKP Cullin F-Box Protein Ligases
  • CDC2 Protein Kinase
  • GTP-Binding Proteins
  • Peptide Synthases
  • Nocodazole