ERK and cell death: mechanisms of ERK-induced cell death--apoptosis, autophagy and 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 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 functions.
Cagnol
Sebastien
S
Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada. sebcagnol@yahoo.fr
Chambard
Jean-Claude
JC
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D053181:Caspase 8 / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology; D045304:Cytochromes c / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000502:physiology; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D048490:raf Kinases / Q000502:physiology; D018631:ras Proteins / Q000502:physiology
D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D045304:Cytochromes c; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D053181:Caspase 8; D018631:ras Proteins