A 2-Cys peroxiredoxin regulates peroxide-induced oxidation and activation of a stress-activated MAP kinase

Mol Cell. 2004 Jul 2;15(1):129-39. doi: 10.1016/j.molcel.2004.06.021.


Oxidative stress-induced cell damage is an important component of many diseases and ageing. In eukaryotes, activation of JNK/p38 stress-activated protein kinase (SAPK) signaling pathways is critical for the cellular response to stress. 2-Cys peroxiredoxins (2-Cys Prx) are highly conserved, extremely abundant antioxidant enzymes that catalyze the breakdown of peroxides to protect cells from oxidative stress. Here we reveal that Tpx1, the single 2-Cys Prx in Schizosaccharomyces pombe, is required for the peroxide-induced activation of the p38/JNK homolog, Sty1. Tpx1 activates Sty1, downstream of previously identified redox sensors, by a mechanism that involves formation of a peroxide-induced disulphide complex between Tpx1 and Sty1. We have identified conserved cysteines in Tpx1 and Sty1 that are essential for normal peroxide-induced Tpx1-Sty1 disulphide formation and Tpx1-dependent regulation of peroxide-induced Sty1 activation. Thus we provide new insight into the response of SAPKs to diverse stimuli by revealing a mechanism for SAPK activation specifically by oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Base Sequence / genetics
  • Binding Sites / physiology
  • Cysteine / metabolism*
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Hydrogen Peroxide / pharmacology
  • Macromolecular Substances
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Molecular Sequence Data
  • Oxidants / pharmacology
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Peroxidases / genetics
  • Peroxidases / isolation & purification
  • Peroxidases / metabolism*
  • Peroxiredoxins
  • Protein Binding / physiology
  • Schizosaccharomyces / enzymology
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Signal Transduction / physiology
  • Sulfides / metabolism


  • Macromolecular Substances
  • Oxidants
  • Schizosaccharomyces pombe Proteins
  • Sulfides
  • Tpx1 protein, S pombe
  • Hydrogen Peroxide
  • Peroxidases
  • Peroxiredoxins
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinases
  • sty1 protein, S pombe
  • Cysteine

Associated data

  • SWISSPROT/074887