fig1

Figure 1. Summary of wild-type and mutant p53 calcium mediated cell death processes. (A) Wild-type p53: (1) induces apoptosis by different cellular stresses such as hypoxia and chemotherapy; (2) mediates an increase in ER Ca²⁺ through SERCA; (3) promotes ER Ca²⁺ transfer to the mitochondria resulting in a Ca²⁺ overloading activated caspase 3 and thus PARP; and (4) mediates apoptosis through an induction in TRPC6 expression and (5) associated Ca²⁺ influx. (B) (1) Mutations in TP53 result in a loss of function; (2) TP53 fails to induce SERCA; (3) this leads to reduced mitochondrial Ca²⁺ promoting apoptotic resistance; (4) ORAI3 is increased in TNBC, promoting Ca²⁺-mediated increase in serum and glucocorticoid-induced protein kinase-1 (SGK-1) inducing TP53 degradation and (5) increased S100 calcium-binding protein P (S100P) also induces TP53 degradation. Both enhance cell survival. ER: Endoplasmic reticulum; PARP: poly(ADP-Ribose) polymerase; SERCA: sarco/endoplasmic reticulum Ca²⁺ ATPase.