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Characterization of Sep15, a novel thioredoxin‐like selenoprotein, and its interaction with UDP‐glucose:glycoprotein glucosyltransferase
Author(s) -
Labunskyy Vyacheslav M,
Ferguson Andrew D,
Fomenko Dmitri E,
Chelliah Yogarany,
Hatfield Dolph L,
Gladyshev Vadim N
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a428-b
Subject(s) - protein disulfide isomerase , biochemistry , selenoprotein , endoplasmic reticulum , chemistry , chaperone (clinical) , microbiology and biotechnology , biology , enzyme , glutathione peroxidase , superoxide dismutase , medicine , pathology
Selenium is an important trace element with potent cancer prevention activity. The 15‐kDa selenoprotein (Sep15) has been proposed to mediate the chemopreventive effect of dietary selenium. Although the precise function of Sep15 remains elusive, UDP‐glucose:glycoprotein glucosyltransferase (GT), an endoplasmic reticulum chaperone involved in assessing fidelity of protein folding, was identified as the binding partner of Sep15. In this study we used co‐immunoprecipitation and isothermal titration calorimetry to characterize interactions between members of GT and Sep15 protein families. Sep15 and GT formed a tight 1:1 complex, and this interaction was mediated by a novel cysteine‐rich domain located at the N‐terminus of Sep15. We also measured redox potential of Sep15, which is similar to that of protein disulfide isomerase suggesting that the C‐terminal domain that contains a redox active CxU motif may be involved in the formation and isomerization of disulfide bonds. In mammals, Sep15 expression was regulated by dietary selenium, and either increased expression or depletion of Sep15 by RNA interference altered redox homeostasis. Taken together, these observations suggest that Sep15 may link cancer preventive effects of selenium and the quality control machinery of the endoplasmic reticulum. This work was supported by a NIH grant CA080946.