Txl1 and Txc1 are co-factors of the 26S proteasome in fission yeast

TY - JOUR

T1 - Txl1 and Txc1 are co-factors of the 26S proteasome in fission yeast

AU - Andersen, Katrine M

AU - Jensen, Camilla

AU - Kriegenburg, Franziska

AU - Lauridsen, Anne-Marie B

AU - Gordon, Colin

AU - Hartmann-Petersen, Rasmus

PY - 2011/5/1

Y1 - 2011/5/1

N2 - 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.

AB - 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.

KW - Humans

KW - Microscopy, Fluorescence

KW - Polymerase Chain Reaction

KW - Proteasome Endopeptidase Complex

KW - Protein Binding

KW - Schizosaccharomyces

KW - Schizosaccharomyces pombe Proteins

KW - Thioredoxins

U2 - 10.1089/ars.2010.3329

DO - 10.1089/ars.2010.3329

M3 - Journal article

C2 - 21091378

SN - 1523-0864

VL - 14

SP - 1601

EP - 1608

JO - Antioxidants & Redox Signaling

JF - Antioxidants & Redox Signaling

IS - 9

ER -