The abundance of Met30p limits SCF(Met30p) complex activity and is regulated by methionine availability.
Ubiquitin-mediated degradation plays a crucial role in many fundamental biological pathways, including the mediation of cellular responses to changes in environmental conditions. A family of ubiquitin ligase complexes, called SCF complexes, found throughout eukaryotes, is involved in a variety of biological pathways. In Saccharomyces cerevisiae, an SCF complex contains a common set of components, namely, Cdc53p, Skp1p, and Hrt1p. Substrate specificity is defined by a variable component called an F-box protein. The F- box is a approximately 40-amino-acid motif that allows the F-box protein to bind Skp1p. Each SCF complex recognizes different substrates according to which F-box protein is associated with the complex. In yeasts, three SCF complexes have been demonstrated to associate with the ubiquitin-conjugating enzyme Cdc34p and have ubiquitin ligase activity. F-box proteins are not abundant and are unstable. As part of the SCF(Met30p) complex, the F-box protein Met30p represses methionine biosynthetic gene expression when availability of L-methionine is high. Here we demonstrate that in vivo SCF(Met30p) complex activity can be regulated by the abundance of Met30p. Furthermore, we provide evidence that Met30p abundance is regulated by the availability of L-methionine. We propose that the cellular responses mediated by an SCF complex are directly regulated by environmental conditions through the control of F-box protein stability.
Smothers
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DB
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Kozubowski
L
L
Dixon
C
C
Goebl
M G
MG
Mathias
N
N
D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D044842:Cullin Proteins; D044783:F-Box Proteins; D005434:Flow Cytometry; D005982:Glutathione Transferase / Q000378:metabolism; D008025:Ligases / Q000737:chemistry / Q000378:metabolism; D008715:Methionine / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010453:Peptide Synthases / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044786:S-Phase Kinase-Associated Proteins; D044843:SKP Cullin F-Box Protein Ligases; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D019089:Stem Cell Factor / Q000378:metabolism*; D013379:Substrate Specificity; D013696:Temperature; D013997:Time Factors; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D001616:beta-Galactosidase / Q000378:metabolism
C100988:Cdc53 protein, S cerevisiae; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; D044783:F-Box Proteins; C470285:MET30 protein, S cerevisiae; D012097:Repressor Proteins; D044786:S-Phase Kinase-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D019089:Stem Cell Factor; D008715:Methionine; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; C485632:HRT1 protein, S cerevisiae; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; D005982:Glutathione Transferase; D001616:beta-Galactosidase; D008025:Ligases; D010453:Peptide Synthases