Figure 8. Proposed mechanisms of enhanced cell death following inhibition of p53. Shown are the effects of p53 suppression on components of cell death pathways in Pif + VMY vs. VMY treated D556 cells. p53 inhibition by Pifithrin resulted in the induction of p63 and p73 genes and subsequent enhanced cell death via apoptosis. Induction of the p63 and p73 genes leads to the activation of p211 and p27KIP1 both of which can indirectly trigger FADD, reducing the expression of BIRC3 (cIAP2). Induction of p73 led to large increases in EndoG and CIDEB expression leading to DNA fragmentation while increased levels of p63 induced apoptosis though BIRC3 and BIK, the latter of which along with TRPM8 can influence intracellular calcium levels. BAD; BCL2-Associated Agonist Of Cell Death, BIK; BCL2-Interacting Killer (Apoptosis-Inducing), BIRC3; baculoviral IAP repeat containing 3 (cIAP2), BRAT1; BRCA1-Associated ATM Activator 1, CAPN; Calpain, CALB1; Calbindin 1, CDKN2D; Cyclin-Dependent Kinase Inhibitor 2D (p19Ink4D), CIDEB; Cell Death-Inducing DFFA-Like Effector B, EndoG; Endonuclease G, FADD; Fas-Associated Via Death Domain, INCA1; Inhibitor Of CDK, Cyclin A1 Interacting Protein 1, NF-KappaB; Nuclear Factor Of Kappa Light Polypeptide Gene Enhancer In B-Cells, TRPM8, Transient receptor potential cation channel subfamily M member 8.