The SCFSkp2 ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation

Xianghong Li, Qiping Zhao, Rong Liao, Peiqing Sun, Xiaohua Wu

Research output: Contribution to journalArticlepeer-review

Abstract

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 SCFSkp2 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 SCFSkp2-mediated ubiquitination pathway may play an important role in the cell cycle-dependent Cdt1 degradation in mammalian cells.

Original languageEnglish (US)
Pages (from-to)30854-30858
Number of pages5
JournalJournal of Biological Chemistry
Volume278
Issue number33
DOIs
StatePublished - Aug 15 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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