| First Author | Xia Y | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 26 | Pages | 17428-37 |
| PubMed ID | 19395378 | Mgi Jnum | J:151205 |
| Mgi Id | MGI:4352995 | Doi | 10.1074/jbc.M109.007823 |
| Citation | Xia Y, et al. (2009) Loss of Wip1 sensitizes cells to stress- and DNA damage-induced apoptosis. J Biol Chem 284(26):17428-37 |
| abstractText | 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 damage-induced 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. |
