Glucose and Ras activity influence the ubiquitin ligases APC/C and SCF in Saccharomyces cerevisiae

Ln budding yeast, the Ras/cAMP pathway is involved in the coordination of c ell growth and cell division. Glucose-rich medium stimulates Ras/cAMP signa ling, which causes an increase in the critical cell size for cell cycle ent ry. Here we show that glucose and activated Ras proteins also influence the function of the anaphase-promoting complex (APC/C),a ubiquitin-protein lig ase required for sister chromatid separation and mitotic exit. We found tha t apc10-22 and other mutants defective in the APC/G are suppressed by reduc ed Ras signaling activity, by a deletion of the RAS2 gene, by a cdc25 mutat ion, by elevated levels of PDE2, or by growth without glucose. Viability of these mutants is also enhanced by decreased Cdk1 activity. In contrast, a constitutively activated RAS2(Vali9) allele or shifts to glucose medium are deleterious to apc10-22 mutants. Remarkably, cdc34-2 mutants, which are im paired in SCF function, are differently affected with respect to Ras activi ty. Viability of cdc34-2 mutants at elevated temperatures is dependent on g lucose and the RAS2 gene. We conclude that glucose and Ras proteins influen ce the APC/C and the SCF complex in an opposite manner. These ubiquitin lig ases might represent novel targets for modulating cell division in response to growth conditions.