GSBS Student Publications

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Molecular Genetics and Microbiology

Date

3-30-2007

Document Type

Article

Medical Subject Headings

Cell Nucleus; Conserved Sequence; DNA Damage; Escherichia coli; Eukaryotic Cells; Gene Expression Regulation; Humans; Hydrogen Peroxide; Intracellular Signaling Peptides and; Proteins; Multigene Family; *Oxidative Stress; Protein Structure, Tertiary; Proteins; Tumor Cells, Cultured

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

CONCLUSION: 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.

Rights and Permissions

Citation: BMC Cell Biol. 2007 Mar 28;8:13. Link to article on publisher's site

Related Resources

Link to article in PubMed

Journal Title

BMC cell biology

PubMed ID

17391516

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