title: 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.
abstract: 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.
authors.affiliation: Friedrich Miescher Institut, Basel, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Lisztwan
authors.forename: A
authors.initials: A
authors.lastname: Marti
authors.forename: H
authors.initials: H
authors.lastname: Sutterlüty
authors.forename: M
authors.initials: M
authors.lastname: Gstaiger
authors.forename: C
authors.initials: C
authors.lastname: Wirbelauer
authors.forename: W
authors.initials: W
authors.lastname: Krek
mesh_terms: D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D000906:Antibodies / Q000737:chemistry; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D044842:Cullin Proteins; D019925:Cyclin A / Q000378:metabolism; D019143:Evolution, Molecular; D015801:Helminth Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D046912:Multiprotein Complexes; D017434:Protein Structure, Tertiary; D044786:S-Phase Kinase-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
chemical_list: D000906:Antibodies; D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D019925:Cyclin A; D015801:Helminth Proteins; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D044786:S-Phase Kinase-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; C577449:CDC34 protein, S cerevisiae; C577447:CDC34 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D007930:Leucine