The Circadian Clock in Cancer Development and Therapy - Progress in Molecular Biology and Translational Science - page 252

Figure 9.3 Circadian control of intracellular signaling. The central pacemaker controlled
autonomic nervous and neuroendocrine systems (ANS and NES) rhythmically signal
to all of their target tissues. The resulting circadian rhythm in peripheral tissue function
also generates local and/or circulating signaling molecules that rhythmically act on their
targets. Together, these extracellular signals including neurotransmitters, steroid hor-
mones, peptide hormones, chemokines, growth factors, and cytokines activate intracel-
lular signaling mediated by G-protein-coupled receptors (GPCRs), tyrosine kinase
receptors, integrins (not shown), and nuclear receptors in a tissue and cell type-specific
manner. These same intracellular signaling pathways also activate the peripheral clock.
The coordinated activities of the central and peripheral clocks orchestrate the compli-
cated extracellular and intracellular signaling to maintain tissue homeostasis by control-
ling a network of gene expression. Disruption of the central clock-controlled
extracellular signaling or mutations in core circadian genes both abolish peripheral
clock activity leading to loss of circadian homeostasis in peripheral tissues. The