title: Ubiquitination and degradation of the substrate recognition subunits of SCF ubiquitin-protein ligases.
abstract: The S. cerevisiae SCFCdc4p ubiquitin-protein ligase complex promotes cell cycle transitions through degradation of cell cycle regulators. To investigate SCFCdc4p regulation in vivo, we examined the stability of individual SCFCdc4p components. Whereas Cdc53p and Skp1p were stable, Cdc4p, the F box-containing component responsible for substrate recognition, was short lived and subject to SCF-mediated ubiquitination. Grr1p, another F box component of SCF complexes, was also ubiquitinated. A stable truncated Cdc4pF-beta-gal hybrid protein capable of binding Skp1p and entering into an SCF complex interfered with proteolysis of SCF targets and inhibited cell proliferation. The finding that the F box-containing SCF components are unstable suggests a mechanism of regulating SCF function through ubiquitination and proteolysis of F box components.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: P
authors.initials: P
authors.lastname: Zhou
authors.forename: P M
authors.initials: PM
authors.lastname: Howley
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D017489:CDC28 Protein Kinase, S cerevisiae / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D044842:Cullin Proteins; D016213:Cyclins / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D044783:F-Box Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006207:Half-Life; D006918:Hydroxyurea / Q000494:pharmacology; D008025:Ligases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008074:Lipoproteins / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D015739:Nocodazole / Q000494:pharmacology; D010675:Pheromones; D011233:Precipitin Tests; D046988:Proteasome Endopeptidase Complex; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism
chemical_list: C080443:CDC4 protein, S cerevisiae; C082721:CLN2 protein, S cerevisiae; D002352:Carrier Proteins; C100988:Cdc53 protein, S cerevisiae; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; D016213:Cyclins; D044783:F-Box Proteins; D005656:Fungal Proteins; D008074:Lipoproteins; C095063:MFA2 protein, S cerevisiae; D009097:Multienzyme Complexes; D010675:Pheromones; D011993:Recombinant Fusion Proteins; D044786:S-Phase Kinase-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; C071032:GRR1 protein, S cerevisiae; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D017489:CDC28 Protein Kinase, S cerevisiae; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases; D015739:Nocodazole; D006918:Hydroxyurea