The OXR domain defines a conserved family of eukaryotic oxidation resistance proteins.
BACKGROUND
The NCOA7 gene product is an estrogen receptor associated protein that is highly similar to the human OXR1 gene product, which functions in oxidation resistance. OXR genes are conserved among all sequenced eukaryotes from yeast to humans. In this study we examine if NCOA7 has an oxidation resistance function similar to that demonstrated for OXR1. We also examine NCOA7 expression in response to oxidative stress and its subcellular localization in human cells, comparing these properties with those of OXR1.


RESULTS
We find that NCOA7, like OXR1 can suppress the oxidative mutator phenotype when expressed in an E. coli strain that exhibits an oxidation specific mutator phenotype. Moreover, NCOA7's oxidation resistance function requires expression of only its carboxyl-terminal domain and is similar in this regard to OXR1. We find that, in human cells, NCOA7 is constitutively expressed and is not induced by oxidative stress and appears to localize to the nucleus following estradiol stimulation. These properties of NCOA7 are in striking contrast to those of OXR1, which is induced by oxidative stress, localizes to mitochondria, and appears to be excluded, or largely absent from nuclei.


CONCLUSIONS
NCOA7 most likely arose from duplication. Like its homologue, OXR1, it is capable of reducing the DNA damaging effects of reactive oxygen species when expressed in bacteria, indicating the protein has an activity that can contribute to oxidation resistance. Unlike OXR1, it appears to localize to nuclei and interacts with the estrogen receptor. This raises the possibility that NCOA7 encodes the nuclear counterpart of the mitochondrial OXR1 protein and in mammalian cells it may reduce the oxidative by-products of estrogen metabolite-mediated DNA damage.
Durand
Mathieu
M
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. math_dur@hotmail.com <math_dur@hotmail.com>
Kolpak
Adrianne
A
Farrell
Timothy
T
Elliott
Nathan A
NA
Shao
Wenlin
W
Brown
Myles
M
Volkert
Michael R
MR
D002467:Cell Nucleus / Q000378:metabolism; D017124:Conserved Sequence; D004249:DNA Damage; D004926:Escherichia coli; D005057:Eukaryotic Cells; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D024101:Mitochondrial Proteins; D005810:Multigene Family; D056918:Nuclear Receptor Coactivators; D018384:Oxidative Stress; D017434:Protein Structure, Tertiary / Q000502:physiology; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured
D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; C455500:NCOA7 protein, human; D056918:Nuclear Receptor Coactivators; C419777:OXR1 protein, human; D011506:Proteins; D006861:Hydrogen Peroxide