The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation

J Biol Chem. 2003 Aug 15;278(33):30854-8. doi: 10.1074/jbc.C300251200. Epub 2003 Jul 2.


DNA replication initiation is tightly controlled so that each origin only fires once per cell cycle. Cell cycle-dependent Cdt1 degradation plays an essential role in DNA replication control, as overexpression of Cdt1 leads to re-replication. In this study, we investigated the mechanisms of Cdt1 degradation in mammalian cells. We showed that the F-box protein Skp2 specifically interacted with human Cdt1 in a phosphorylation-dependent manner. The SCF(Skp2) complex ubiquitinated Cdt1 both in vivo and in vitro. Down-regulation of Skp2 or disruption of the interaction between Cdt1 and Skp2 resulted in a stabilization and accumulation of Cdt1. These results suggest that the SCF(Skp2)-mediated ubiquitination pathway may play an important role in the cell cycle-dependent Cdt1 degradation in mammalian cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cysteine Endopeptidases / metabolism
  • DNA Replication / physiology*
  • G1 Phase / physiology
  • Humans
  • In Vitro Techniques
  • Ligases / genetics
  • Ligases / metabolism*
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / metabolism
  • Mutagenesis
  • Phosphorylation
  • Proteasome Endopeptidase Complex
  • S Phase / physiology
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases


  • CDT1 protein, human
  • Cell Cycle Proteins
  • Multienzyme Complexes
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Ligases