Figure 5. Circadian period–altering compounds target multiple signaling pathways.

(A) Interaction network (PPI enrichment P-value 3.04 × 10⁻⁷) among phosphoproteins (green) and kinases (blue) modulated by circadian period–altering compounds. siRNA knockdown of the candidates highlighted with a golden yellow dot induces long period length in circadian oscillations (>26 h at least in one of the two independent siRNA pairs). siRNA knockdown data obtained from BioGPS circadian layout database (http://biogps.gnf.org/circadian/) (Zhang et al, 2009). Core clock (red) and additional clock (pink) components are also integrated into the network. Association network is generated using the STRING database involving only high confidence (score > 0.8) interactions. (B) Signaling pathways associated with the phosphoproteins and kinases altered by circadian period–modulating compounds (analysed using IPA, top 15, FDR < 0.05). (C) Interaction network among the signaling pathways associated with the phosphoproteins and kinases altered by circadian period–modulating compounds.