Figure 7.

Schematic representation of how CLK8 affects CLOCK and the circadian rhythm. CLOCK and BMAL1 interact dynamically. CLK8 binds to CLOCK and reduces the CLOCK-BMAL1 interaction. When CLK8 binds to CLOCK, the translocation of CLOCK into the nucleus is abolished. CLK8 enhances the amplitude of the circadian rhythm at the cellular level, so the role of CLOCK in regulating the circadian clock amplitude can be investigated using CLK8 to transiently modulate CLOCK. The thin line indicates reduction in the strength of the positive arm of the transcription/translation feedback loop (TTFL); the thick line indicates enhanced strength in the negative arm of the TTFL.