Phosphorylation and stabilization of TAp63γ by IκB kinase-β

Post-translational modification of the p53 family members is key to their regulation. Here we report the phosphorylation of TAp63 gamma, but not Delta Np63 gamma, by I kappa B kinase beta (IKK beta). Activation of IKK beta by gamma radiation or tumor necrosis factor-alpha led to increased TAp63 gamma protein levels in cells. IKK beta, but not its kinase-defective mutant IKK beta-K44A, led to this observed stabilization of TAp63 gamma. This stabilization of TAp63 gamma in response to gamma radiation was significantly decreased in the absence of IKK beta. Phosphorylation of TAp63 gamma blocks ubiquitylation and possible degradation of this protein. We postulate that phosphorylation of TAp63 gamma by IKK beta stabilizes the TAp63 gamma protein by blocking ubiquitylation-dependent degradation of this protein.