Cdc53 targets phosphorylated G1 cyclins for degradation by the ubiquitin proteolytic pathway.
In budding yeast, cell division is initiated in late G1 phase once the Cdc28 cyclin-dependent kinase is activated by the G1 cyclins Cln1, Cln2, and Cln3. The extreme instability of the Cln proteins couples environmental signals, which regulate Cln synthesis, to cell division. We isolated Cdc53 as a Cln2-associated protein and show that Cdc53 is required for Cln2 instability and ubiquitination in vivo. The Cln2-Cdc53 interaction, Cln2 ubiquitination, and Cln2 instability all depend on phosphorylation of Cln2. Cdc53 also binds the E2 ubiquitin-conjugating enzyme, Cdc34. These findings suggest that Cdc53 is a component of a ubiquitin-protein ligase complex that targets phosphorylated G1 cyclins for degradation by the ubiquitin-proteasome pathway.
Willems
A R
AR
Programme in Molecular Biology and Cancer Samuel Lunenfeld Research Institute Mount Sinai Hospital, Toronto, Canada.
Lanker
S
S
Patton
E E
EE
Craig
K L
KL
Nason
T F
TF
Mathias
N
N
Kobayashi
R
R
Wittenberg
C
C
Tyers
M
M
D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D044842:Cullin Proteins; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000378:metabolism; D016193:G1 Phase; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*
C082719:CLN1 protein, S cerevisiae; C082721:CLN2 protein, S cerevisiae; C079895:CLN3 protein, S cerevisiae; C100988:Cdc53 protein, S cerevisiae; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; D016213:Cyclins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; C577449:CDC34 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D018844:Cyclin-Dependent Kinases; D008025:Ligases