Figure 7. Spring-loaded activation mechanism of TAp63α on the molecular and cellular level.
(A) Schematic energy landscape of TAp63α. The kinetically trapped closed dimer is opened by phosphorylation or artificially by moderate concentrations of urea (Figure 4). The resulting open dimer is less stable and forms tetramers with a dissociation constant of 12 ± 1 nM (Brandt et al., 2009). (B) Schematic representation of TAp63α activation. Oocytes express high levels of dimeric TAp63α and harbor normally inactive kinases ready to be activated and to phosphorylate TAp63α upon genotoxic stress leading to active tetramers and, consequently, cell death.