Fig. 5

Mortalin is the contextual determinant of p53 (TP53) nucleocytoplasmic shuttling. (1) Cytoplasmic p53 is sequestered by the heat shock protein mortalin in cancer cells through multiple mechanisms, including excess nuclear export of p53, defective cytoplasmic degradation, retention by cytoskeletal proteins and other potential mechanisms. (2) Glycogen synthase kinase-3 beta (GSK-3beta) phosphorylates p53 to induce its cytoplasmic localization, thereby enhancing constitutive cytoplasmic localization of p53 under ER stress to prevent p53 stabilization and p53-mediated apoptosis upon DNA damage [76]