Fuzzy interactions between the auto-phosphorylated C-terminus and the kinase domain of CK1δ inhibits activation of TAp63α.

ABSTRACT: The p53 family member TAp63α plays an important role in maintaining the genetic integrity in oocytes. DNA damage, in particular DNA double strand breaks, lead to the transformation of the inhibited, only dimeric conformation into the active tetrameric one that results in the initiation of an apoptotic program. Activation requires phosphorylation by the kinase CK1 which phosphorylates TAp63α at four positions. The third phosphorylation event is the decisive step that transforms TAp63α into the active state. This third phosphorylation, however, is ~ 20 times slower than the first two phosphorylation events. This difference in the phosphorylation kinetics constitutes a safety mechanism that allows oocytes with a low degree of DNA damage to survive. So far these kinetic investigations of the p

SUBMITTER: Lambert M 

PROVIDER: S-EPMC10542812 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature