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. 2022 Nov 9;25(12):105546. doi: 10.1016/j.isci.2022.105546

Figure 7.

Figure 7

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.