Figure 7. Model of FRQ phosphorylation and interactome.
Symbol size represents abundance of FRQ or relative steady-state interaction of FRH, WCC and CKI with FRQ. FRQ and FRH are always in a complex regardless of FRQ levels or phosphorylation. Slightly after subjective dawn, as frq mRNA levels reach a maximum, FRQ and CK1 interaction peaks, phase-lagging WCC interaction. In the subjective day as total FRQ levels increase, interaction with the WCC decreases. During this phase, the C-terminal region of FRQ is at its maximum relative phosphorylation state, helping to stabilize FRQ. During the subjective evening/night phosphorylation of the PEST-1 domain increases thereby destabilizing FRQ and interaction with the WCC is minimal. Approaching subjective dawn FRQ becomes fully phosphorylated, is degraded, and frq expression is reinitiated. New, hypophosphorylated, FRQ immediately associates with FRH and quickly increases its interaction level with the WCC to start a new cycle.