Separate SCF(CDC4) recognition elements target Cdc6 for proteolysis in S phase and mitosis.

The Cdc6 DNA replication initiation factor is targeted for ubiquitin-mediated proteolysis by the E3 ubiquitin ligase SCF(CDC4) from the end of G1phase until mitosis in the budding yeast Saccharomyces cerevisiae. Here we describe a dominant-negative CDC6 mutant that, when overexpressed, arrests the cell cycle by inhibiting cyclin-dependent kinases (CDKs) and, ...
thus, prevents passage through mitosis. This mutant protein inhibits CDKs more efficiently than wild-type Cdc6, in part because it is completely refractory to SCF(CDC4)-mediated proteolysis late in the cell cycle and consequently accumulates to high levels. The mutation responsible for this phenotype destroys a putative CDK phosphorylation site near the middle of the Cdc6 primary amino acid sequence. We show that this site lies within a novel Cdc4-interacting domain distinct from a Cdc4-interacting site identified previously near the N-terminus of the protein. We show that both sites can target Cdc6 for proteolysis in late G1/early S phase whilst only the newly identified site can target Cdc6 for proteolysis during mitosis.
Mesh Terms:
Amino Acid Sequence, Base Sequence, Binding Sites, Cell Cycle, Cell Cycle Proteins, Cyclin-Dependent Kinases, DNA Primers, F-Box Proteins, Fungal Proteins, Galactose, Genotype, Glucose, Mitosis, Nocodazole, Phosphorylation, Promoter Regions, Genetic, S Phase, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Suppression, Genetic, Ubiquitin-Protein Ligases
EMBO J.
Date: Sep. 03, 2001
Download Curated Data For This Publication
19877
Switch View:
  • Interactions 1
  • PTM Genes 1