Fig. 2
From: Cisplatin based therapy: the role of the mitogen activated protein kinase signaling pathway
Illustration of MAPK pathway and the role of cisplatin in promoting apoptosis or cell survival. Cisplatin-induced ERK activation phosphorylates p53 which in turn upregulates expression of p21, 45kd-growth arrest and DNA damage (GADD45), and mouse double minute 2 homolog (Mdm2) thereby promoting cell cycle arrest and supporting repair of DNA damage induced by cisplatin. ERK also activates its downstream mediator, RSK which promotes cell survival and metastasis. Cisplatin induced DNA damage activates JNK and p73 and promotes their complex formation and leads to apoptosis. Cisplatin induces stabilization of p18 (Hamlet), a protein regulated by p38 MAPK. This enhances the ability of p53 to interact with and activate pro-apoptotic genes, PUMA and NOXA