Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation

Nat Cell Biol. 1999 May;1(1):14-9. doi: 10.1038/8984.


The transcription factor E2F-1 is important in the control of cell proliferation. Its activity must be tightly regulated in a cell-cycle-dependent manner to enable programs of gene expression to be coupled closely with cell-cycle position. Here we show that, following its accumulation in the late G1 phase of the cell cycle, E2F-1 is rapidly degraded in S/G2 phase. This event is linked to a specific interaction of E2F-1 with the F-box-containing protein p45SKP2, which is the cell-cycle-regulated component of the ubiquitin-protein ligase SCFSKP2 that recognizes substrates for this ligase. Disruption of the interaction between E2F-1 and p45SKP2 results in a reduction in ubiquitination of E2F-1 and the stabilization and accumulation of transcriptionally active E2F-1 protein. These results indicate that an SCFSKP2-dependent ubiquitination pathway may be involved in the downregulation of E2F-1 activity in the S/G2 phase of the cell cycle, and suggest a link between SCFSKP2 and cell-cycle-dependent gene control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Carrier Proteins*
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • G1 Phase
  • G2 Phase
  • HeLa Cells
  • Homeostasis
  • Humans
  • Kinetics
  • Ligases / metabolism*
  • Mice
  • Retinoblastoma-Binding Protein 1
  • S Phase
  • S-Phase Kinase-Associated Proteins
  • Substrate Specificity
  • Transcription Factor DP1
  • Transcription Factors / metabolism*
  • Ubiquitin-Protein Ligases
  • Ubiquitins / metabolism


  • Arid4a protein, mouse
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • E2f1 protein, mouse
  • Retinoblastoma-Binding Protein 1
  • S-Phase Kinase-Associated Proteins
  • Transcription Factor DP1
  • Transcription Factors
  • Ubiquitins
  • Ubiquitin-Protein Ligases
  • Ligases