Peroxiredoxin IV is an endoplasmic reticulum localised enzyme forming oligomeric complexes in human cells
Résumé
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 oligomeric state. Of the human peroxiredoxins, Prx IV is unique in possessing an N-terminal signal peptide believed to allow secretion from the cell. Here we present a characterisation of Prx IV in human cells demonstrating that it is actually retained within the endoplasmic reticulum. Stable knockdown of Prx IV expression led to detrimental effects upon viability of human HT1080 cells following treatment with exogenous hydrogen peroxide. 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 hydrogen peroxide turnover. Subsequent investigation demonstrated Prx IV to form complex structures within the ER consistent with the formation of homodecamers. Furthermore, Prx IV oligomeric interactions are stabilised by additional non-catalytic disulphide bonds indicative of a primary role other than peroxide elimination.
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