Journal
EMBO REPORTS
Volume 11, Issue 8, Pages 633-639Publisher
WILEY
DOI: 10.1038/embor.2010.82
Keywords
p63; Cables1; proteasome; oocyte; apoptosis
Categories
Funding
- Massachusetts General Hospital
- National Institute on Aging [R37-AG012279]
- National Institutes of Health [R01-CA098333]
- Henry and Vivian Rosenberg Philanthropic Fund
- Sea Breeze Foundation
- Vincent Memorial Research Funds
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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) p63 alpha 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 TAp63 alpha and reduced accumulation of phosphorylated TAp63 alpha 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.
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