Fig. 8

Scr1 and Rst2 co-function with Tup/Ssn6 to coordinate CCR in S. pombe. The Scr1 repressor (blue) and the Rst2 activator (red) comprise two downstream effectors of the glucose signal in S. pombe. In the glucose condition, nuclear localized Scr1 binds to and enforces the repression of genes involved in carbohydrate utilization, hexose transport, glucose signaling, glycolysis and the TCA cycle. Under these conditions the Git3-Gpa2-Git2 glucose sensing machinery is also active and sustains intracellular cAMP levels via Cyr1, in turn maintaining PKA in an active state via Cgs1 inhibition resulting in the hyper-phosphorylation and inactivation of Rst2. In the absence of glucose, Scr1 is inactivated by the Ssp2 AMPK [17], Cgs2 (purple) is subsequently upregulated and drives the conversion of intracellular cAMP to AMP [51]. This removes cAMP mediated inhibition of the PKA regulatory module Cgs1, allowing inhibition of PKA activity. In turn, Rst2 becomes active and replaces Scr1 at the promoter of the majority of Scr1 target genes as well as genes involved in gluconeogenesis and sexual differentiation. (Fig. 5c). Tup11 (green), a component of the Tup/Ssn6 co-regulator, co-localises at gene promoters with both Scr1 and Rst2 regardless of carbon condition thus playing a role in both the repression and activation of gene expression in response to glucose