Delayed accumulation of the yeast G1 cyclins Cln1 and Cln2 and the F-box protein Grr1 in response to glucose

The ability to integrate nutrient availability into cell cycle regulation is critical for the viability of organisms. The Saccharomyces cerevisiae ubiquitin ligase SCF(Grr1) regulates the stability of several proteins that participate in cell division or nutrient sensing. Two of its targets, the cyclins Cln1 and Cln2, accumulate in the presence of glucose. When glucose is added to cells growing asynchronously, we show that the accumulation of the cyclins is a very slow response. We report that the F-box protein Grr1 also accumulates at higher levels in the presence of glucose, and that the response to glucose follows a delayed pattern strikingly similar to that described for Cln1 and Cln2. A model for the regulation of F-box proteins predicts that substrate accumulation could stabilize Grr1. While we found that Grr1 is more stable in cells growing with glucose, we show that the delayed responses to glucose occur independently: Grr1 accumulates in the absence of the cyclins, and vice versa. Thus, our results indicate that this model might not apply to the cyclins and Grr1. Glucose is known to strengthen the interaction of Grr1 with Skp1 in the SCF complex. We hypothesize that glucose could promote the accumulation of Grr1 and its assembly into a SCF complex as a feedback regulation that helps compensate for higher cyclins levels.