Wip1 contributes to cell homeostasis maintained by the steady-state level of Wtp53
Volume 10, Issue 15
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August 1, 2011
Pages 2574 - 2582http://dx.doi.org/10.4161/cc.10.15.15923
Authors: Hwan Ki Park, Jayabal Panneerselvam, Fred Duafalia Dudimah, Guangzhi Dong, Sinto Sebastian, Jun Zhang and Peiwen Fei View affiliations
Wip1, a human protein Ser/Thr phosphatase also called PPM1D, stands for wild type p53 induced phosphatase 1. Emerging evidences indicate that Wip1 can act as an oncogene largely by turning off DNA damage checkpoint responses. Here we report an unrecognized role of Wipl in normally growing cells. Wip1 can be induced by wild type p53 under not only stressed but also non-stressed conditions. It can trigger G2/M arrest in wild type p53 containing cells, which was attributed to the decreased Cdc2 kinase activity resulting at least partly from a high level of inhibitory tyrosine phosphorylation on Cdc2 protein at Tyr-15. Furthermore, we also found that Wip1 not only causes G2/M arrest but also decreases cell death triggered by microtubule assembly inhibitor in mouse fibroblasts when wild type p53 function was restored. These results indicate that Wip1 can provide ample time for wild type p53-containing cells to prepare entry into mitosis and avoid encountering mitotic catastrophe. Therefore, Wipl may play important roles in cell/tissue homeostasis maintained by wild type p53 under normal conditions, enhancing our understanding of how p53 makes cell-fate decisions.
Received: April 10, 2011; Accepted: June 8, 2011