Quality control in oocytes by p63 is based on a spring-loaded activation mechanism on the molecular and cellular level.

ABSTRACT: Mammalian oocytes are arrested in the dictyate stage of meiotic prophase I for long periods of time, during which the high concentration of the p53 family member TAp63α sensitizes them to DNA damage-induced apoptosis. TAp63α is kept in an inactive and exclusively dimeric state but undergoes rapid phosphorylation-induced tetramerization and concomitant activation upon detection of DNA damage. Here we show that the TAp63α dimer is a kinetically trapped state. Activation follows a spring-loaded mechanism not requiring further translation of other cellular factors in oocytes and is associated with unfolding of the inhibitory structure that blocks the tetramerization interface. Using a combination of biophysical methods as well as cell and ovary culture experiments we explain how TAp63α is kept

SUBMITTER: Coutandin D 

PROVIDER: S-EPMC4876613 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature