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Publication : p38alpha MAP kinase as a sensor of reactive oxygen species in tumorigenesis.

First Author  Dolado I Year  2007
Journal  Cancer Cell Volume  11
Issue  2 Pages  191-205
PubMed ID  17292829 Mgi Jnum  J:118334
Mgi Id  MGI:3699447 Doi  10.1016/j.ccr.2006.12.013
Citation  Dolado I, et al. (2007) p38alpha MAP kinase as a sensor of reactive oxygen species in tumorigenesis. Cancer Cell 11(2):191-205
abstractText  p38alpha is a stress-activated protein kinase that negatively regulates malignant transformation induced by oncogenic H-Ras, although the mechanisms involved are not fully understood. Here, we show that p38alpha is not a general inhibitor of oncogenic signaling, but that it specifically modulates transformation induced by oncogenes that produce reactive oxygen species (ROS). This inhibitory effect is due to the ROS-induced activation of p38alpha early in the process of transformation, which induces apoptosis and prevents the accumulation of ROS and their carcinogenic effects. Accordingly, highly tumorigenic cancer cell lines have developed a mechanism to uncouple p38alpha activation from ROS production. Our results indicate that oxidative stress sensing plays a key role in the inhibition of tumor initiation by p38alpha.
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