Two distinct ubiquitin-proteolysis pathways in the fission yeast cell cycle

The SCF complex (Skp1-Cullin-1-F-box) and the APC/cyclosome (anaphase-promo ting complex) are two ubiquitin ligases that play a crucial role in eukaryo tic cell cycle control. In fission yeast F-box/WD-repeat proteins Pop1 and Pop2, components of SCF are required for cell-cycle-dependent degradation o f the cyclin-dependent kinase (CDK) inhibitor Rum1 and the S-phase regulato r Cdc18. Accumulation of these proteins in pop1 and pop2 mutants leads to r e-replication and defects in sexual differentiation. Despite structural and functional similarities, Pop1 and Pop2 are not redundant homologues. Inste ad, these two proteins form heterodimers as well as homodimers, such that t hree distinct complexes, namely SCFPop1/Pop1, SCFPop1/Pop2 and SCFPop2/Pop2 , appear to exist in the cell. The APC/cyclosome is responsible for inactiv ation of CDK/cyclins through the degradation of B-type cyclins. We have ide ntified two novel components or regulators of this complex, called Apc10 an d Ste9, which are evolutionarily highly conserved. Apc10 (and Ste9), togeth er 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 univer sal mechanism that is used to arrest the cell cycle at G1.