title: Txl1 and Txc1 are co-factors of the 26S proteasome in fission yeast.
abstract: The 26S proteasome is a large proteolytic particle present in the cytosol and nucleus of eukaryotic cells. Most intracellular proteins, including those affected by oxidative damage, are degraded by the proteasome. The human thioredoxin, Txnl1, is known to associate with the 26S proteasome and thereby equips proteasomes with redox capabilities. Here, we characterize the fission yeast orthologue of Txnl1, called Txl1. Txl1 associates with the 26S proteasome via its C-terminal domain. This domain is also found in the uncharacterized protein, Txc1, which was also found to interact with 26S proteasomes. A txl1 null mutant, but not a txc1 null, displayed a synthetic growth defect with cut8, encoding a protein that tethers the proteasome to the nuclear membrane. Txc1 is present throughout the cytoplasm and nucleus, whereas Txl1 co-localizes with 26S proteasomes in both wild-type cells and in cut8 mutants, indicating that Txl1 is tightly associated with 26S proteasomes, while Txc1 might be only transiently bound to the complex. Finally, we show that Txl1 is an active thioredoxin. Accordingly, Txl1 was able to reduce and mediate the degradation of an oxidized model proteasome substrate in vitro. Thus, Txl1 and Txc1 are proteasome co-factors connected with oxidative stress.
authors.affiliation: Department of Biology, University of Copenhagen, Denmark.
authors.forename: Katrine M
authors.initials: KM
authors.lastname: Andersen
authors.forename: Camilla
authors.initials: C
authors.lastname: Jensen
authors.forename: Franziska
authors.initials: F
authors.lastname: Kriegenburg
authors.forename: Anne-Marie B
authors.initials: AM
authors.lastname: Lauridsen
authors.forename: Colin
authors.initials: C
authors.lastname: Gordon
authors.forename: Rasmus
authors.initials: R
authors.lastname: Hartmann-Petersen
mesh_terms: D006801:Humans; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013879:Thioredoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D029702:Schizosaccharomyces pombe Proteins; C504766:TXNL1 protein, human; D013879:Thioredoxins; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease