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Cables1 protects p63 from proteasomal degradation to ensure deletion of cells after genotoxic stress
Author(s) -
Wang Ning,
Guo Lankai,
Rueda Bo R,
Tilly Jonathan L
Publication year - 2010
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2010.82
Subject(s) - ubiquitin , microbiology and biotechnology , gene isoform , germline , biology , dna damage , kinase , mutant , cancer research , gene , genetics , dna
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.