Association of human CUL-1 and ubiquitin-conjugating enzyme CDC34 with the F-box protein p45(SKP2): evidence for evolutionary conservation in the subunit composition of the CDC34-SCF pathway.
In normal and transformed cells, the F-box protein p45(SKP2) is required for S phase and forms stable complexes with p19(SKP1) and cyclin A-cyclin-dependent kinase (CDK)2. Here we identify human CUL-1, a member of the cullin family, and the ubiquitin-conjugating enzyme CDC34 as additional partners of p45(SKP2) in vivo. CUL-1 also ... associates with cyclin A and p19(SKP1) in vivo and, with p45(SKP2), they assemble into a large multiprotein complex. In Saccharomyces cerevisiae, a complex of similar molecular composition (an F-box protein, a member of the cullin family and a homolog of p19(SKP1)) forms a functional E3 ubiquitin protein ligase complex, designated SCFCDC4, that facilitates ubiquitination of a CDK inhibitor by CDC34. The data presented here imply that the p45(SKP2)-CUL-1-p19(SKP1) complex may be a human representative of an SCF-type E3 ubiquitin protein ligase. We propose that all eukaryotic cells may use a common ubiquitin conjugation apparatus to promote S phase. Finally, we show that multiprotein complex formation involving p45(SKP2)-CUL-1 and p19(SKP1) is governed, in part, by periodic, S phase-specific accumulation of the p45(SKP2) subunit and by the p45(SKP2)-bound cyclin A-CDK2. The dependency of p45(SKP2)-p19(SKP1) complex formation on cyclin A-CDK2 may ensure tight coordination of the activities of the cell cycle clock with those of a potential ubiquitin conjugation pathway.
Mesh Terms:
Amino Acid Sequence, Animals, Antibodies, Cell Cycle, Cell Cycle Proteins, Cell Line, Cullin Proteins, Cyclin A, Evolution, Molecular, Helminth Proteins, Humans, Leucine, Ligases, Macromolecular Substances, Mice, Molecular Sequence Data, Multigene Family, Multiprotein Complexes, Protein Structure, Tertiary, S-Phase Kinase-Associated Proteins, Sequence Homology, Amino Acid, Transfection, Tumor Cells, Cultured, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases
Amino Acid Sequence, Animals, Antibodies, Cell Cycle, Cell Cycle Proteins, Cell Line, Cullin Proteins, Cyclin A, Evolution, Molecular, Helminth Proteins, Humans, Leucine, Ligases, Macromolecular Substances, Mice, Molecular Sequence Data, Multigene Family, Multiprotein Complexes, Protein Structure, Tertiary, S-Phase Kinase-Associated Proteins, Sequence Homology, Amino Acid, Transfection, Tumor Cells, Cultured, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases
EMBO J.
Date: Jan. 15, 1998
PubMed ID: 9430629
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