PER-dependent rhythms in CLK phosphorylation and E-box binding regulate circadian transcription

Transcriptional activation by CLOCK-CYCLE (CLK-CYC) heterodimers is influenced by interactions with PERIOD-TIMELESS (PER-TIM) heterodimers.

• PER-TIM interacts with CLK-CYC, inhibiting CLK-CYC's binding to E-box regulatory elements in living organisms.
• This interaction is associated with the hyperphosphorylation of CLK.
• DOUBLE-TIME (DBT) kinase enters a complex with CLK-CYC, which destabilizes both CLK and PER.
• After degradation of PER and CLK, a novel hypophosphorylated form of CLK accumulates.
• Accumulation of this CLK form coincides with E-box binding and transcriptional activation.
• The findings suggest that PER influences CLK phosphorylation rhythms, affecting transcription and CLK stability.

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