Mechanisms of nuclear localization of glutathione reductase, subnuclear colocalization with thioredoxin, and genetic analysis of a chemically induced glutathione reductase knockout
Year: 2004
Type: article
Abstract: Glutathione reductase [GR; EC 1.6.4.2] is a ubiquitous, highly conserved protein that has been identified in plants, bacteria, yeast, and mammals.GR expressions and functions in cytosol and mitochondria have been studied, but little is known about mechanisms of import or functions of GR within the nucleus.No classical nuclear localization signal has been identified in GR, but cDNAs containing either mitochondrial targeting signals (MTS) from human MnSOD or from human GR (hGR) target GR transgene products to both the mitochondria and the nucleus.In contrast, cells transfected with a construct coding for a hGR-MTS/GFP fusion protein demonstrated fluorescence only in the mitochondria.Subsequent mutational deletion analyses of the hGR MTS indicated a tight correlation between nuclear and mitochondrial levels of expression and with the numbers of amino acids in the truncated MTSs.The MTS is necessary but not sufficient for nuclear localization of GR.Microscopy studies of cells in culture revealed GR-dependent immunofluorescence in subnuclear clusters.Subsequent investigations indicated that the GR-containing clusters do not colocalize with proteins found in subnuclear structures that exhibit morphologies similar to the anti-GR immunoreactive forms, or with p-histone 3, a protein involved in replication.In both native and transfected cells, GR was colocalized with glutaredoxin, and I wish to thank my advisor Skip Smith for intellectual support and encouragement.
Author: Lynette K. Rogers
Institution: The Ohio State University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2475289522