Recently, Wip1 was found to be expressed in intestinal stem cells and to inhibit p53-mediated apoptosis, which promotes tumor initiation (65). Thus, abrogation of functionality of the tumor suppressor p53 by Wip1 in constantly proliferating intestinal stem cells of the APCmin mouse model was sufficient to induce cancerous stem cells or cancer initiating stem cells, which was demonstrated to be the origin of intestinal cancer (81) (Figure 5B). In contrast, continuous activation of the stress response in stem cells lacking Wip1 also had an effect on the life span of stem cells. For instance, the neural stem/progenitor cell (NPC) population in Wip1-deficient mice was significantly reduced in the subventricular zone (SVZ), which is where the NPCs normally reside. Consequently, the neural stemness (especially toward neurogenesis) was lowered, and this was shown to be dependent on p53 (91). On the other hand, human mesenchymal stem cells (hMSCs) undergo premature senescence in culture due to accumulated oxidative stress and/or constant DNA damage signaling (92, 93) (unpublished data). Stable expression of Wip1 in hMSCs lowers the stress response and overcomes premature senescence, which
