Institute of Molecular and Cell Biology, Cell Cycle Control and Tumorigenesis Group, 61 Biopolis Drive, Proteos, Singapore.
Trends Biochem Sci. 2010 Feb;35(2):109-14. doi: 10.1016/j.tibs.2009.09.005. Epub 2009 Oct 29.
The PP2C family serine/threonine phosphatase WIP1 is characterized by distinctive oncogenic properties mediated by inhibitory functions on several tumor suppressor pathways, including ATM, CHK2, p38MAPK and p53. PPM1D, the gene encoding WIP1, is aberrantly amplified in different types of human primary cancers, and its deletion in mice results in a profound tumor-resistant phenotype. Numerous downstream targets of WIP1 have been identified, and genetic studies confirm that some play a part in tumorigenesis. Recent evidence highlights a new role for WIP1 in the regulation of a cell-autonomous decline in proliferation of certain self-renewing cell types, including pancreatic beta-cells, with advancing age. These emerging functions of WIP1 make it a potent therapeutic target against cancer and aging.
PP2C 家族丝氨酸/苏氨酸磷酸酶 WIP1 的特征在于其通过抑制多种肿瘤抑制途径（包括 ATM、CHK2、p38MAPK 和 p53）的抑制功能介导的独特致癌特性。编码 WIP1 的基因 PPM1D 在不同类型的人类原发性癌症中异常扩增，其在小鼠中的缺失导致明显的肿瘤抵抗表型。已经鉴定出 WIP1 的许多下游靶标，遗传研究证实其中一些靶标在肿瘤发生中起作用。最近的证据强调了 WIP1 在调节某些自我更新细胞类型（包括胰岛β细胞）增殖的自主衰退中的新作用，随着年龄的增长而衰退。WIP1 的这些新功能使其成为对抗癌症和衰老的有效治疗靶点。
