APC(ste9/srw1) promotes degradation of mitotic cyclins in G(1) and is inhibited by cdc2 phosphorylation

EMBO J. 2000 Aug 1;19(15):3945-55. doi: 10.1093/emboj/19.15.3945.


Fission yeast ste9/srw1 is a WD-repeat protein highly homologous to budding yeast Hct1/Cdh1 and Drosophila Fizzy-related that are involved in activating APC/C (anaphase-promoting complex/cyclosome). We show that APC(ste9/srw1) specifically promotes the degradation of mitotic cyclins cdc13 and cig1 but not the S-phase cyclin cig2. APC(ste9/srw1) is not necessary for the proteolysis of cdc13 and cig1 that occurs at the metaphase-anaphase transition but it is absolutely required for their degradation in G(1). Therefore, we propose that the main role of APC(ste9/srw1) is to promote degradation of mitotic cyclins when cells need to delay or arrest the cell cycle in G(1). We also show that ste9/srw1 is negatively regulated by cdc2-dependent protein phosphorylation. In G(1), when cdc2-cyclin kinase activity is low, unphosphorylated ste9/srw1 interacts with APC/C. In the rest of the cell cycle, phosphorylation of ste9/srw1 by cdc2-cyclin complexes both triggers proteolysis of ste9/srw1 and causes its dissociation from the APC/C. This mechanism provides a molecular switch to prevent inactivation of cdc2 in G(2) and early mitosis and to allow its inactivation in G(1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anaphase-Promoting Complex-Cyclosome
  • CDC2 Protein Kinase / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Cell Differentiation
  • Conserved Sequence
  • Cyclin B / metabolism
  • Cyclins / metabolism*
  • Drosophila Proteins
  • Fungal Proteins / metabolism
  • G1 Phase / physiology*
  • Ligases / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Kinases / metabolism
  • Schizosaccharomyces / cytology*
  • Schizosaccharomyces pombe Proteins*
  • Ubiquitin-Protein Ligase Complexes*
  • Ubiquitin-Protein Ligases


  • Cell Cycle Proteins
  • Cig1 protein, S pombe
  • CycB protein, Drosophila
  • Cyclin B
  • Cyclins
  • Drosophila Proteins
  • Fungal Proteins
  • Schizosaccharomyces pombe Proteins
  • srw1 protein, S pombe
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Ubiquitin-Protein Ligases
  • Protein Kinases
  • CDC2 Protein Kinase
  • Ligases