SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box.
We have identified the yeast and human homologs of the SKP1 gene as a suppressor of cdc4 mutants and as a cyclin F-binding protein. Skp1p indirectly binds cyclin A/Cdk2 through Skp2p, and directly binds Skp2p, cyclin F, and Cdc4p through a novel structural motif called the F-box. SKP1 is required for ubiquitin-mediated proteolysis of Cin2p, Clb5p, and the Cdk inhibitor Sic1p, and provides a link between these molecules and the proteolysis machinery. A large number of proteins contain the F-box motif and are thereby implicated in the ubiquitin pathway. Different skp1 mutants arrest cells in either G1 or G2, suggesting a connection between regulation of proteolysis in different stages of the cycle.
Bai
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Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
Sen
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Hofmann
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Ma
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Goebl
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Harper
J W
JW
Elledge
S J
SJ
D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome; D001483:Base Sequence; D001665:Binding Sites / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D016213:Cyclins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; D005656:Fungal Proteins / Q000502:physiology; D016193:G1 Phase / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D018628:Gene Dosage; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008025:Ligases / Q000235:genetics; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation / Q000502:physiology; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D016196:S Phase / Q000502:physiology; D044786:S-Phase Kinase-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000502:physiology*; D015003:Yeasts / Q000235:genetics
C503669:CCNF protein, human; C082721:CLN2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D016213:Cyclins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D005656:Fungal Proteins; D011506:Proteins; D044786:S-Phase Kinase-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D008025:Ligases