Fig. 3.

Mechanism of glucose repression and induction. Glucose is transported into the cell by Hxt transporters with diverse affinities. Intracellular glucose is converted to glucose-6-phosphate primarily by Hxk2p and then fermented to ethanol and CO₂ (5). Snf1p protein kinase is one of the main players in glucose repression and the induction pathway; it regulates the activities of TFs of glucose repression genes (Mig1p) and gluconeogenesis (Cat8p-Sip4p and Adr1p). In the presence of glucose, Snf1 is deactivated by the phosphatase, Glc7p-Reg1p, in a Hxk2p-dependent manner (15). Once inhibition by Snf1p is released, Mig1p is phosphorylated, enters the nucleus, and represses the expression of alternative carbon source utilization genes (e.g., GAL4, SUC2, SNF3, and gluconeogenesis TF genes CAT8 and SIP5) (5). Iron uptake and transport genes are induced throughout Snf1p/Snf4p and the TF Rcs1p, independent of iron starvation (22). A separate sensing pathway mediates glucose induction of mainly glucose transporter genes. Extracellular glucose binds to glucose receptors Snf3p or Rgt2p (with high and low affinities, respectively) to generate a signal that inactivates the transcriptional receptor Rgt1p. This signal induces the HXT genes, MIG2, and its own activators, STD1 and MTH1 (29, 16). The glucose signal inhibits Rgt1p-mediated expression by stimulating the degradation of Mth1p and Std1p (28). The two pathways, Snf1-Mig1 and Rgt1, are interconnected in both protein signaling and transcriptional levels mainly throughout Mth1p and Hxk2p, which are regulated by both Mig1p and Rgt1p (18, 30) and have a signaling role in the pathways. In addition, Mig1p regulates one of the sensors of the Rgt1 pathway, Snf3p, where Rgt1p regulates the transporters that bring the Snf1 pathway into action. Another glucose sensing and signaling mechanism, not shown here, is responsible for activation of ribosomal and glycolysis genes and repression of glycogen, trehalose, and stress genes through Gpr1p, cAMP, and PKA (4).