Taken together, these studies describe a mechanism by which p53 inhibits Wip1 expression – through induction of miR-16. However, this is contrary to the previously demonstrated induction of Wip1 by p53 after DNA damage (3, 19). The differences may reflect cell type-specific differences in miR-16 expression levels or the complex temporal regulation of Wip1 expression. Indeed, Zhang et al. emphasized that miR-16 reduced Wip1 protein levels at early times after NCS addition, but later, miR-16 expression was reduced, and both p53 and Wip1 protein levels continued to increase (36). The p53-dependent inhibition of Wip1 expression through increased miR-16 levels may be an important mechanism that prevents tumorigenesis, since Wip1 promotes tumorigenesis and miR-16 has tumor suppressor properties (10, 18, 37–39).
