Oxidative stress is the most powerfully specific stress activating p38 MAPK. Abnormal activity (higher or lower than physiological) of p38 has been implicated in pathological stresses in several tissues, that include neuronal, bone, lung, cardiac and skeletal muscle, red blood cells, and fetal tissues. The protein product of
proto-oncogene RAS can increase activity of p38, and thereby cause excessively high activity of transcription factor NF-κB. This transcription factor is normally regulated from intracellular pathways that integrate signals from the surrounding tissue and the immune system. In turn these signals coordinate between cell survival and cell death. Dysregulated NF-κB activity can activate genes that cause cancer cell survival, and can also activate genes that facilitate cancer cell metastasis to other tissues. P38 was also shown to correlate with outcome of
glioblastoma - higher pathway activity is associated with low survival. == Inhibitors ==