Cables1 protects p63 from proteasomal degradation to ensure deletion of cells after genotoxic stress.
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) p63alpha 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 TAp63alpha and reduced accumulation of phosphorylated TAp63alpha 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.
Wang
Ning
N
Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA.
Guo
Lankai
L
Rueda
Bo R
BR
Tilly
Jonathan L
JL
D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D005260:Female; D005854:Germ Cells / Q000166:cytology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
C411580:Cables1 protein, mouse; D002352:Carrier Proteins; D016213:Cyclins; D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D046988:Proteasome Endopeptidase Complex