TAp63α is a member of the p53 family of proteins, which also includes p53 and p73: these proteins are all transcription factors, so they need to be able to bind to DNA (bottom row). Some mutant forms of p53 can contribute to cancer phenotypes by binding to the C-terminal of normal p53 and p73 proteins: however, these mutant forms cannot bind to TAp63α dimers (because C-terminal regions of the dimers are not accessible). Phosphorylation (blue dots) is the trigger for activation of all three family members, but the mechanism is different for each. For p53 (left) phosphorylation mainly inhibits degradation by proteasomes, thus promoting stabilization of the protein; for TAp73α (right) phosphorylation affects the DNA binding affinity; and for TAp63α (middle) phosphorylation enables the opening up of dimers, which are inactive, in order to form tetramers, which are active. Acetylation (green dots) is also involved in the activation of p53 and TAp73α.