title: Two distinct ubiquitin-proteolysis pathways in the fission yeast cell cycle.
abstract: The SCF complex (Skp1-Cullin-1-F-box) and the APC/cyclosome (anaphase-promoting complex) are two ubiquitin ligases that play a crucial role in eukaryotic cell cycle control. In fission yeast F-box/WD-repeat proteins Pop1 and Pop2, components of SCF are required for cell-cycle-dependent degradation of the cyclin-dependent kinase (CDK) inhibitor Rum1 and the S-phase regulator Cdc18. Accumulation of these proteins in pop1 and pop2 mutants leads to re-replication and defects in sexual differentiation. Despite structural and functional similarities, Pop1 and Pop2 are not redundant homologues. Instead, these two proteins form heterodimers as well as homodimers, such that three distinct complexes, namely SCFPop1/Pop1, SCFPop1/Pop2 and SCFPop2/Pop2, appear to exist in the cell. The APC/cyclosome is responsible for inactivation of CDK/cyclins through the degradation of B-type cyclins. We have identified two novel components or regulators of this complex, called Apc10 and Ste9, which are evolutionarily highly conserved. Apc10 (and Ste9), together with Rum1, are required for the establishment of and progression through the G1 phase in fission yeast. We propose that dual downregulation of CDK, one via the APC/cyclosome and the other via the CDK inhibitor, is a universal mechanism that is used to arrest the cell cycle at G1.
authors.affiliation: Laboratory of Cell Regulation, Imperial Cancer Research Fund, London, UK. toda@europa.lif.icnet.uk
authors.forename: T
authors.initials: T
authors.lastname: Toda
authors.forename: I
authors.initials: I
authors.lastname: Ochotorena
authors.forename: K
authors.initials: K
authors.lastname: Kominami
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D002453:Cell Cycle; D006801:Humans; D008025:Ligases / Q000378:metabolism*; D010453:Peptide Synthases / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases; D012568:Schizosaccharomyces / Q000201:enzymology*; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D014452:Ubiquitins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D010453:Peptide Synthases