tailieunhanh - Báo cáo khoa học: ERK and cell death: Mechanisms of ERK-induced cell death – apoptosis, autophagy and senescence

The Ras⁄Raf⁄extracellular signal-regulated kinase (ERK) signaling path-way plays a crucial role in almost all cell functions and therefore requires exquisite control of its spatiotemporal activity. Depending on the cell type and stimulus, ERK activity will mediate different antiproliferative events, such as apoptosis, autophagy and senescence in vitro and in vivo. | MINIREVIEW ERK and cell death Mechanisms of ERK-induced cell death - apoptosis autophagy and senescence Sebastien Cagnol1 and Jean-Claude Chambard2 1 Department of Anatomy and Cellular Biology Faculty of Medicine and Health Sciences University of Sherbrooke Canada 2 Institute of DevelopmentalBiology and Cancer University of Nice France Keywords apoptosis autophagy DUSP ERK ROS senescence The Ras Raf extracellular signal-regulated kinase ERK signaling pathway plays a crucial role in almost all cell functions and therefore requires exquisite control of its spatiotemporal activity. Depending on the cell type Correspondence S. Cagnol Department of Anatomy and Cellular Biology Faculty of Medicine and Health Sciences University of Sherbrooke Sherbrooke Quebec Canada Fax 1 819 564 5320 Tel 1 819 820 6868 ext. 15715 E-mail sebcagnol@ and stimulus ERK activity will mediate different antiproliferative events such as apoptosis autophagy and senescence in vitro and in vivo. ERK activity can promote either intrinsic or extrinsic apoptotic pathways by induction of mitochondrial cytochrome c release or caspase-8 activation permanent cell cycle arrest or autophagic vacuolization. These unusual effects require sustained ERK activity in specific subcellular compartments and could depend on the presence of reactive oxygen species. We will summarize the mechanisms involved in Ras Raf ERK antiproliferative Received 18 June 2009 revised 26 August 2009 accepted 9 September 2009 functions. doi Ras Raf ERK the pathway ERK2 ERK1 also known as p42 p44MAPK respectively and officially named MAPK 1 and 3 are two isoforms of extracellular signal-regulated kinase ERK that belong to the family of mitogen-activated protein kinases MAPKs which include ERK5 the c-Jun-NH2-terminal kinases JNK1 2 3 and the p38 MAP kinases p38 a p s y . These enzymes are activated through a sequential phosphorylation cascade that amplifies and transduces signals from the cell .