title: The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation.
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 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.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Li
authors.forename: Qiping
authors.initials: Q
authors.lastname: Zhao
authors.forename: Rong
authors.initials: R
authors.lastname: Liao
authors.forename: Peiqing
authors.initials: P
authors.lastname: Sun
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004261:DNA Replication / Q000502:physiology*; D016193:G1 Phase / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D016296:Mutagenesis; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D016196:S Phase / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: C467199:CDT1 protein, human; D018797:Cell Cycle Proteins; D009097:Multienzyme Complexes; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases