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However, ectopic WWOX has no effect with U87-MG expressing wild type p53. Unlike TMZ, WWOX induces apoptosis of U373-MG cells via a mitochondria-independent and caspase-3-independent pathway (Chiang et al., 2012). While the underlying mechanisms are unknown, it is reasonable to assume that the survival of human glioblastoma cells depends upon interactions between the gain-of-function of p53 mutants and WWOX. Activated WWOX binds wild type p53 with Ser46 phosphorylation (Chang et al., 2005b). UV irradiation enhances the binding interactions. Despite the presence of Ser46 in Δ40p53, binding of this protein with WWOX remains to be determined. We postulate that in GBM cells, both wild type p53 and ectopic WWOX proteins appear to have a functional antagonism, thereby nullifying each other’s function in inducing apoptosis (Figure 2). Mutant p53 proteins cannot bind ectopic WWOX in GBM cells, and WWOX is able to induce apoptosis. 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