APC(ste9/srw1) promotes degradation of mitotic cyclins in G(1) and is inhibited by cdc2 phosphorylation.
Fission yeast ste9/srw1 is a WD-repeat protein highly homologous to budding yeast Hct1/Cdh1 and Drosophila Fizzy-related that are involved in activating APC/C (anaphase-promoting complex/cyclosome). We show that APC(ste9/srw1) specifically promotes the degradation of mitotic cyclins cdc13 and cig1 but not the S-phase cyclin cig2. APC(ste9/srw1) is not necessary for the proteolysis of cdc13 and cig1 that occurs at the metaphase-anaphase transition but it is absolutely required for their degradation in G(1). Therefore, we propose that the main role of APC(ste9/srw1) is to promote degradation of mitotic cyclins when cells need to delay or arrest the cell cycle in G(1). We also show that ste9/srw1 is negatively regulated by cdc2-dependent protein phosphorylation. In G(1), when cdc2-cyclin kinase activity is low, unphosphorylated ste9/srw1 interacts with APC/C. In the rest of the cell cycle, phosphorylation of ste9/srw1 by cdc2-cyclin complexes both triggers proteolysis of ste9/srw1 and causes its dissociation from the APC/C. This mechanism provides a molecular switch to prevent inactivation of cdc2 in G(2) and early mitosis and to allow its inactivation in G(1).
Instituto de Microbiología Bioquímica, Departamento de Microbiología y Genética, CSIC/Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
M A
MA
Blanco
A
A
Sánchez-Díaz
J M
JM
de Prada
S
S
Moreno
D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D017124:Conserved Sequence; D019926:Cyclin B / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D029721:Drosophila Proteins; D005656:Fungal Proteins / Q000378:metabolism; D016193:G1 Phase / Q000502:physiology*; D008025:Ligases / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology*; D029702:Schizosaccharomyces pombe Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
D018797:Cell Cycle Proteins; C095858:Cig1 protein, S pombe; C503698:CycB protein, Drosophila; D019926:Cyclin B; D016213:Cyclins; D029721:Drosophila Proteins; D005656:Fungal Proteins; D029702:Schizosaccharomyces pombe Proteins; C113000:srw1 protein, S pombe; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D011494:Protein Kinases; D016203:CDC2 Protein Kinase; D008025:Ligases