Figure 3.

Restoration of p53 pathway signaling in canonical and non-canonical regulatory pathways in cancer cells. Cellular stresses activate p53 pathway signaling through p53 transactivation (canonical pathway, left panel). The p53 pathway signaling is regulated via p73, a p53 family member (such as by NSC59984), or via ATF4 (induction by small molecules such as PG3-Oc and CB002) in mutant p53-expressing cancer cells (non-canonical regulatory pathways, right panel). The gene expression via ATF4 or p73 partially overlaps with the canonical p53 targets, and some of the overlapping canonical p53 pathway signaling target genes (such as Noxa, PUMA, and p21) are crucial for the compounds to induce cell death and cell cycle arrest under different cellular conditions.