Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC

Cell. 2003 Apr 4;113(1):101-13. doi: 10.1016/s0092-8674(03)00232-0.

Abstract

Entry into mitosis requires the activation of cdk1/cyclin B, while mitotic exit is achieved when the same kinase activity decreases, as cyclin B is degraded. Cyclin B proteolysis is mediated by the anaphase promoting complex, or APC, an E3 ligase that is active at anaphase in mitosis through G1. We have identified a G1 substrate of the APC that we have termed Tome-1, for trigger of mitotic entry. Tome-1 is a cytosolic protein required for proper activation of cdk1/cyclin B and mitotic entry. Tome-1 associates with Skp-1 and is required for degradation of the cdk1 inhibitory tyrosine kinase wee1; Tome-1 therefore appears to be acting as part of an SCF-type E3 for wee1. Degradation of Tome-1 during G1 allows for wee 1 accumulation during interphase, thereby providing a critical link between the APC and SCF pathways in regulation of cdk1/cyclin B activity and thus mitotic entry and exit.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / isolation & purification*
  • Cell Cycle Proteins / metabolism
  • Cyclin B / genetics
  • Cyclin B / metabolism*
  • Cytosol / metabolism
  • DNA, Complementary / analysis
  • DNA, Complementary / genetics
  • Eukaryotic Cells / metabolism*
  • G1 Phase / genetics*
  • HeLa Cells
  • Humans
  • Ligases / genetics
  • Ligases / metabolism*
  • Mice
  • Mitosis / genetics*
  • Molecular Sequence Data
  • Nuclear Proteins*
  • Phosphorylation
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • S-Phase Kinase-Associated Proteins
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Ubiquitin / genetics
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligase Complexes*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / isolation & purification*

Substances

  • CDCA3 protein, Xenopus
  • CDCA3 protein, human
  • Cell Cycle Proteins
  • Cyclin B
  • DNA, Complementary
  • Nuclear Proteins
  • S-Phase Kinase-Associated Proteins
  • Tome-1 protein, mouse
  • Ubiquitin
  • Xenopus Proteins
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Protein-Tyrosine Kinases
  • WEE1 protein, human
  • Wee1 protein, mouse
  • CDC2 Protein Kinase
  • Ligases