Figure 5
From: JNK–NQO1 axis drives TAp73-mediated tumor suppression upon oxidative and proteasomal stress
JNK stabilizes TAp73 by Nrf2–NQO1 axis, which is synthetic lethal with TAp73 phosphorylation. (a) TAp73 is stabilized in HCT116TP53−/− and H1299 cells pretreated for 1 h with WA as shown by CHX chase experiment. (b) WA facilitates TAp73/NQO1 binding as revealed by co-immunoprecipitation experiment. (c) NAC prevents the binding of NQO1 to TAp73 promoted by WA and prevents WA-mediated inhibition of MDM2-p73 complex. (d) Accumulation of Ub-tagged TAp73 in WA-treated HCT116TP53−/− cells. (e) Co-expression of MDM2 inhibits TAp73-dependent transactivation in a yeast-based reporter assay, which is partially restored by WA (n=4). (f) In the presence of JNK inhibitor, WA did not inhibit TAp73/MDM2 complex
