A Per2/pGSK3β/β-catenin/Per2 loop in Adaptive Radioprotection (see also Figure S10)
(A) A cluster of β-catenin/TCF/LEF regulated prosurvival effector genes screened with 1.2-fold cutoff in RNAseq profile of Per2wt versus Per2def BMHSCs.
(B) Gene ontology biological process enrichment analysis of up-regulated TCF/LEF targeted genes in Per2wt versus Per2def BMHSCs.
(C) The interaction between four representatives upregulated TCF/LEF targeted genes (1.25-1.52-fold increased expression) with DNA repair genes and mitochondria metabolism genes in Per2wt versus Per2def BMpHSCs performed by VisANT, where k represents the potential KEGG pathways existing.
(D) Schematic pathway of PER2/pGSK3β/β-catenin/PER2 loop in low-dose radiation-induced radioprotection. LDR-induced interaction of PER2 and pGSK3β(Ser9) leading to stabilization of pGSK3β(Ser9) enhancing active β-catenin that enters the nucleus and upregulates Per2 and a cluster of prosurvival genes involved in DNA repair and mitochondrial metabolism via β-catenin/TCF/LEF regulation. Thus, PER2/pGSK3β/β-catenin/PER2 loop may sustain the adaptive cellular homeostasis enhancing cell survival under severe genotoxic condition induced by high dose radiation.