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

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.
Mesh Terms:
3T3 Cells, Animals, Carrier Proteins, Cell Cycle, Cell Cycle Proteins, Cell Line, DNA-Binding Proteins, E2F Transcription Factors, E2F1 Transcription Factor, G1 Phase, G2 Phase, Hela Cells, Homeostasis, Humans, Kinetics, Ligases, Mice, Retinoblastoma-Binding Protein 1, S Phase, S-Phase Kinase-Associated Proteins, Substrate Specificity, Transcription Factor DP1, Transcription Factors, Ubiquitin-Protein Ligases, Ubiquitins
Nat. Cell Biol.
Date: May. 01, 1999
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