Overexpression and short hairpin RNA-mediated depletion of CABLES1 protein resulted in p21(Cip/waf) up- and down-regulation. Aged mice lacking Cables1 displayed abnormalities in peripheral blood cell counts accompanied by a significant reduction in hematopoietic stem cells compartment concomitant with an increased mobilization of progenitor cells.
Agenesis of the corpus callosum frequency in Cables1(+/TAS) mice was significantly lower than that in Cables1(-/TAS) mice indicating that wild-type Cables1 interfered with the dominant negative effect of Cables1(TAS).
Loss of Cables1 enhances tumor progression in the Apc(Min/+) mouse model and activates the Wnt/beta-catenin signaling pathway. Cables1 is a tumor suppressor gene on chromosome 18q in this in vivo mouse model.
Data show that oocytes lacking Cables1 exhibit lower basal levels of TAp63alpha and reduced accumulation of phosphorylated TAp63alpha in response to genotoxic stress.
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