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Chunk #44 — 4. WIP1 SUPPRESSES THE STRESS RESPONSE: UPDATE — 4.4. Functional consequences of Wip1 after stress — 4.4.1. Inhibition of apoptosis

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Regulation of the Wip1 phosphatase and its effects on the stress response.
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correlated with higher levels of activated p53, thus demonstrating that Wip1 inhibits intestinal stem cell apoptosis through inhibition of p53 (65). Furthermore, Kong et al. showed that depletion of Wip1 in MCF-7 breast cancer cells lead to higher levels of apoptosis in response to doxorubicin. This most likely occurs through a p53-dependent mechanism, since these cells also showed higher levels of active p53 and Bax expression (66). Similarly, Parssinen et al. showed that Wip1 depletion by siRNA induced apoptosis in breast cancer cells that had functional p53. This study was done in the absence of exogenous stress, which indicates that Wip1 plays a role in breast cancer cell survival through the inhibition of p53 (67). Therefore, Wip1 inhibition of p53 appears to be a major mechanism by which Wip1 inhibits apoptosis.