RITA (reactivation of p53 and induction of tumor cell apoptosis) binds to p53 (Kd = 1.5 nM), changing its conformation, preventing it from binding to HDM2 (human ortholog of MDM2, Mouse Double-Minute clone 2), and targeting it for proteasomal degradation.1 It also weakly (computed Kd = 22 µM) binds HDM2 in the cleft that contacts the p53 transactivation domain.2 Its restoration of mutant p53 function depends on eIF2alpha phosphorylation, and it induces apoptosis via p53-dependent and -independent (JNK/SAPK/p38, protein translation) pathways.3-5 Induces senescence in head and neck cancer cells.6
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