Characterization of human and mouse peroxiredoxin IV: evidence for inhibition by Prx-IV of epidermal growth factor- and p53-induced reactive oxygen species

Antioxid Redox Signal. 2000 Fall;2(3):507-18. doi: 10.1089/15230860050192288.

Abstract

The aim of this study was to identify and characterize human and mouse Prx-IV. We identified mouse peroxiredoxin IV (Prx-IV) by virtue of sequence homology to its human ortholog previously called AOE372. Mouse Prx-IV conserves an amino-terminal presequence coding for signal peptide. The amino acid sequences of mature mouse and human Prx-IV share 97.5% identity. Phylogenetic analysis demonstrates that Prx-IV is more closely related to Prx-I/-II/-III than to Prx-V/-VI. Previously, we mapped the mouse Prx-IV gene to chromosome X by analyzing two sets of multiloci genetic crosses. Here we performed further comparative analysis of mouse and human Prx-IV genomic loci. Consistent with the mouse results, human Prx-IV gene localized to chromosome Xp22.135-136, in close proximity to SAT and DXS7178. A bacterial artificial chromosome (BAC) clone containing the complete human Prx-IV locus was identified. The size of 7 exons and the sequences of the splice junctions were confirmed by PCR analysis. We conclude that mouse Prx-IV is abundantly expressed in many tissues. However, we could not detect Prx-IV in the conditioned media of NIH-3T3 and Jurkat cells. Mouse Prx-IV was specifically found in the nucleus-excluded region of cultured mouse cells. Intracellularly, overexpression of mouse Prx-IV prevented the production of reactive oxygen species induced by epidermal growth factor or p53. Taken together, mouse Prx-IV is likely a cytoplasmic or organellar peroxiredoxin involved in intracellular redox signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Blotting, Western
  • Chromosome Mapping
  • Cloning, Molecular
  • Culture Media, Conditioned / metabolism
  • Epidermal Growth Factor / antagonists & inhibitors*
  • Exons
  • Humans
  • Jurkat Cells
  • Mice
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Peroxidases / chemistry*
  • Peroxidases / genetics
  • Peroxidases / physiology*
  • Peroxiredoxins
  • Phylogeny
  • Polymerase Chain Reaction
  • Protein Sorting Signals
  • RNA Splicing
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Time Factors
  • Tissue Distribution
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*
  • X Chromosome

Substances

  • Culture Media, Conditioned
  • Protein Sorting Signals
  • RNA, Messenger
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • Epidermal Growth Factor
  • Peroxidases
  • PRDX4 protein, human
  • Peroxiredoxins
  • Prdx4 protein, mouse

Associated data

  • GENBANK/U96746