The role of p38 MAP kinase in cancer cell apoptosis

Many extracellular stimuli are converted into specific cellular responses through the activation of mitogen-activated protein kinase (MAPK) signalling pathways. MAPKs are serine/threonine protein kinases that can phoshorylate both cytoplasmic and nuclear targets.1,2 Four distinct subgroups within the MAP kinase superfamily have been described: extracellular signal-regulated kinases (ERKs), c-jun N-terminal or stress-activated protein kinases (JNK/SAPK), ERK/big MAP kinase 1 (BMK1), and the p38 group of protein kinases.3 The p38 group is in mammals represented by four isoforms (p38α, p38β, p38γ and p38δ) with overlapping but also distinct physiological roles.4 Among them, p38α is the best characterized isoform. Recently, it was observed that retinoids, cisplantin and also other chemoterapeutic agents initiate cancer cell apoptosis through the activation of p38 MAP kinase. This finding connects cancer therapies previously considered to be mechanistically unrelated and raises the possibility of developing anti-cancer agents that Radiol Oncol 2006; 40(1): 51-6.