Mdm-2 Phosphorylation by DNA-dependent Protein Kinase Prevents Interaction with p53

摘要: In response to genotoxic stress, the p53 tumor suppressor protein exerts a G1 cell cycle arrest that is dependent on its ability transactivate downstream target genes. This p53-dependent block reversed by binding of Mdm-2 p53, preventing further transactivation. Interestingly, following DNA damage, mdm-2 gene also transcriptionally activated and therefore, question how can continue genes in presence own negative regulator has remained unanswered. Here, we provide evidence phosphorylation DNA-dependent kinase (DNA-PK) blocks associate with regulate The data support model which DNA-PK activation damage renders unable inhibit transactivation, resulting arrest. Following repair, loss activity results newly synthesized unphosphorylated and, capable allowing progression.