ERK and Cell Death: Mechanisms of ERK-induced Cell Death--Apoptosis, Autophagy and Senescence

FEBS J. 2010 Jan;277(1):2-21. doi: 10.1111/j.1742-4658.2009.07366.x. Epub 2009 Oct 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Autophagy / physiology
  • Caspase 8 / physiology
  • Cell Death / physiology*
  • Cellular Senescence / physiology
  • Cytochromes c / physiology
  • Extracellular Signal-Regulated MAP Kinases / physiology*
  • Humans
  • Lysosomes / physiology
  • MAP Kinase Signaling System
  • Models, Biological
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Reactive Oxygen Species / metabolism
  • Tumor Suppressor Protein p53 / physiology
  • raf Kinases / physiology
  • ras Proteins / physiology

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • Cytochromes c
  • raf Kinases
  • Extracellular Signal-Regulated MAP Kinases
  • Caspase 8
  • ras Proteins