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The  p63  gene product regulates epithelial morphogenesis and female germline integrity. In this study, we show that cyclin‐dependent kinase 5 and Abl enzyme substrate 1 (Cables1) interacts with the  trans ‐activating (TA) p63α isoform to protect it from proteasomal degradation. Using the female germline of  Cables1 ‐null mice as an  in vivo  model, we demonstrate further that oocytes lacking Cables1 exhibit lower basal levels of TAp63α and reduced accumulation of phosphorylated TAp63α in response to genotoxic stress. This in turn enhances the survival of these cells after ionizing radiation exposure. Thus, Cables1 modulates p63 protein stability and function during genotoxic stress.

Cables1 protects p63 from proteasomal degradation to ensure deletion of cells after genotoxic stress