Peroxiredoxin IV is an endoplasmic reticulum-localized enzyme forming oligomeric complexes in human cells

Tavender, T.J., Sheppard, A.M. and Bulleid, N.J. (2008) Peroxiredoxin IV is an endoplasmic reticulum-localized enzyme forming oligomeric complexes in human cells. Biochemical Journal, 411(1), pp. 191-199. (doi:10.1042/BJ20071428)

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Publisher's URL: http://dx.doi.org/10.1042/BJ20071428

Abstract

The peroxiredoxins are a ubiquitous family of proteins involved in protection against oxidative stress through the detoxification of cellular peroxides. In addition, the typical 2-Cys peroxiredoxins function in signalling of peroxide stress and as molecular chaperones, functions that are influenced by their oligomeric state. Of the human peroxiredoxins, Prx IV (peroxiredoxin IV) is unique in possessing an N-terminal signal peptide believed to allow secretion from the cell. Here, we present a characterization of Prx IV in human cells demonstrating that it is actually retained within the ER (endoplasmic reticulum). Stable knockdown of Prx IV expression led to detrimental effects on the viability of human HT1080 cells following treatment with exogenous H<sub>2</sub>O<sub>2</sub>. However, these effects were not consistent with a dose-dependent correlation between Prx IV expression and peroxide tolerance. Moreover, modulation of Prx IV expression showed no obvious effect on ER-associated stress, redox conditions or H<sub>2</sub>O<sub>2</sub> turnover. Subsequent investigation demonstrated that Prx IV forms complex structures within the ER, consistent with the formation of homodecamers. Furthermore, Prx IV oligomeric interactions are stabilized by additional non-catalytic disulfide bonds, indicative of a primary role other than peroxide elimination.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tavender, Dr Timothy and Bulleid, Professor Neil
Authors: Tavender, T.J., Sheppard, A.M., and Bulleid, N.J.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Biochemical Journal
Publisher:Portland Press Ltd.
ISSN:0264-6021
ISSN (Online):1470-8728

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