Characterization of human and mouse peroxiredoxin IV: evidence for inhibition by Prx-IV of epidermal growth factor- and p53-induced reactive oxygen species.
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.
Institute of Molecular Biology, The University of Hong Kong, Pokfulam.
C M
CM
Wong
A C
AC
Chun
K H
KH
Kok
Y
Y
Zhou
P C
PC
Fung
H F
HF
Kung
K T
KT
Jeang
D Y
DY
Jin
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017077:Culture Media, Conditioned / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors*; D005091:Exons; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D054464:Peroxiredoxins; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D021382:Protein Sorting Signals; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*; D014960:X Chromosome
D017077:Culture Media, Conditioned; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D004815:Epidermal Growth Factor; D010544:Peroxidases; C515980:PRDX4 protein, human; D054464:Peroxiredoxins; C515981:Prdx4 protein, mouse