JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species

Free Radic Biol Med. 2006 Mar 15;40(6):928-39. doi: 10.1016/j.freeradbiomed.2005.10.056. Epub 2005 Nov 21.


c-Jun N-terminal kinase (JNK), or stress-activated protein kinase, is an important member of the mitogen-activated protein kinase superfamily, the members of which are readily activated by many environmental stimuli. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are important groups of free radicals that are capable of eliciting direct damaging effects or acting as critical intermediate signaling molecules, leading to oxidative and nitrosative stress and a series of biological consequences. Recently there has been an increasing amount of research interest focusing on the regulatory role of JNK activation in ROS-and RNS-induced cellular responses. In this review we will first summarize and discuss some recent findings regarding the signaling mechanisms of ROS-or RNS-mediated JNK activation. Second, we will talk about the role of JNK in ROS-or RNS-mediated cell death (both apoptosis and necrosis). Finally, we will analyze the emerging evidence for the involvement of ROS and RNS as mediators in tumor necrosis factor alpha-induced apoptosis. Taken together, the accumulating knowledge about the ROS/RNS-induced JNK signaling pathway has greatly advanced our understanding of the complex processes deciding the cellular responses to environmental stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Death / drug effects*
  • Enzyme Activation / drug effects
  • Humans
  • JNK Mitogen-Activated Protein Kinases / physiology*
  • Necrosis / physiopathology
  • Oxidative Stress*
  • Reactive Nitrogen Species / physiology*
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / physiology


  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • JNK Mitogen-Activated Protein Kinases