Figure 2  p53 and WWOX in GBM cell apoptosis. (A) Full-length p53 possesses two N-terminal transactivation acidic domains, a proline-rich domain, a central DNA-binding region, and a C-terminal domain, containing a nuclear localization signal, an oligomerization domain, and a basic region. N-terminal deletion mutants of p53 are also shown. (B) Three likely scenarios are proposed for WWOX and p53 to regulate GBM cell death. First, ectopic WWOX fails to induce apoptosis of GBM cells expressing endogenous wild type p53. It appears that ectopic WWOX binds and functionally antagonizes p53, and both proteins nullify each other’s function in inducing apoptosis. Second, no physical interactions between mutant p53 proteins and WWOX are expected in GBM cells. Thus, ectopic WWOX induce apoptosis in mutant p53-expressing cells. Finally, whether WWOX binds p53 isoforms is unknown. Also, whether ectopic WWOX induction of apoptosis in GBM cells expressing p53 isoforms remains to be established. TAD, transactivation domain; PrD, proline domain; NLS, nuclear localization signal; OD, oligomerization domain; BR, basic region.