WIP1 phosphatase at the crossroads of cancer and aging.
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.
Le Guezennec
Xavier
X
Institute of Molecular and Cell Biology, Cell Cycle Control and Tumorigenesis Group, 61 Biopolis Drive, Proteos, Singapore.
Bulavin
Dmitry V
DV
D000375:Aging / Q000502:physiology*; D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D000071636:Protein Phosphatase 2C
C000607458:PPM1D protein, human; D010749:Phosphoprotein Phosphatases; C000607468:Ppm1d protein, mouse; D000071636:Protein Phosphatase 2C