The regulation of oncogenic Ras/ERK signalling by dual-specificity mitogen activated protein kinase phosphatases (MKPs)

摘要: Dual-specificity MAP kinase (MAPK) phosphatases (MKPs or DUSPs) are well-established negative regulators of MAPK signalling in mammalian cells and tissues. By virtue their differential subcellular localisation ability to specifically recognise, dephosphorylate inactivate different isoforms, they key spatiotemporal pathway activity. Furthermore, as transcriptionally regulated downstream targets can either act classical feedback mediate cross talk between distinct pathways. Because MAPKs particularly Ras/ERK implicated cancer initiation development, the observation that MKPs abnormally human tumours has been interpreted evidence these enzymes suppress promote carcinogenesis. However, definitive such roles lacking. Here we review recent work based on use mouse models, biochemical studies clinical data demonstrate for modulating oncogenic potential also indicate may play a role response certain anticancer drugs. Overall, this reinforces importance regulatory mechanisms activity indicates provide novel therapeutic intervention cancer.