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Title: Loss of Wip1 sensitizes cells to stress- and DNA damage-induced apoptosis
Authors: Xia, Y.
Ongusaha, P.
Lee, S.W.
Liou, Y.-C. 
Issue Date: 26-Jun-2009
Citation: Xia, Y., Ongusaha, P., Lee, S.W., Liou, Y.-C. (2009-06-26). Loss of Wip1 sensitizes cells to stress- and DNA damage-induced apoptosis. Journal of Biological Chemistry 284 (26) : 17428-17437. ScholarBank@NUS Repository.
Abstract: In response to various environmental stresses, the stress-responsive MAPKs p38 and JNK are activated and phosphorylate ATF2 and c-Jun transcription factors, thereby affecting cell-fate decision. Targeted gene disruption studies have established that JNK-c-Jun signaling plays a vital role in stress-induced apoptosis. The oncogenic phosphatase Wip1 acts as an important regulator in DNA damage pathway by dephosphorylating a spectrum of proteins including p53, p38, Chk1, Chk2, and ATM. In this study we show that Wip1 negatively regulates the activation of MKK4-JNK-c-Jun signaling during stress-induced apoptosis. The loss of Wip1 function sensitizes mouse embryonic fibroblasts to stress-induced apoptosis via the activation of both p38- ATF2 and JNK-c-Jun signaling. Here we reveal that Wip1 has dual roles in alternatively regulating stress- and DNA damageinduced apoptosis through p38/JNK MAPKs and p38/p53-dependent pathways, respectively. Our results point to Wip1 as a general regulator of apoptosis, which further supports its role in tumorigenesis. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
ISSN: 00219258
DOI: 10.1074/jbc.M109.007823
Appears in Collections:Staff Publications

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