The Global Transcriptional Activator of Saccharomyces cerevisiae, Gcr1p, Mediates the Response to Glucose by Stimulating Protein Synthesis and CLN-Dependent Cell Cycle Progression

Growth of Saccharomyces cerevisiae requires coordination of cell cycle events (e.g., new cell wall deposition) with constitutive functions like energy generation and duplication of protein mass. The latter processes are stimulated by the phosphoprotein Gcr1p, a transcriptional activator that operates through two different Rap1p-mediated mechanisms to boost expression of glycolytic and ribosomal protein genes, respectively. Simultaneous disruption of both mechanisms results in a loss of glucose responsiveness and a dramatic drop in translation rate. Since a critical rate of protein synthesis (CRPS) is known to mediate passage through Start and determine cell size by modulating levels of Cln3p, we hypothesized that GCR1 regulates cell cycle progression by coordinating it with growth. We therefore constructed and analyzed gcr1(delta) cln3(delta) and gcr1(delta) cln1(delta) cln2(delta) strains. Both strains are temperature and cold sensitive; interestingly, they exhibit different arrest phenotypes. The gcr1(delta) cln3(delta) strain becomes predominantly unbudded with 1N DNA content (G1 arrest), whereas gcr1(delta) cln1(delta) cln2 (delta) cells exhibit severe elongation and apparent M phase arrest. Further analysis demonstrated that the Rap1p/Gcr1p complex mediates rapid growth in glucose by stimulating both cellular metabolism and CLN transcription.