Thioredoxin Txnl1/TRP32 is a redox-active cofactor of the 26 S proteasome.
The 26 S proteasome is a large proteolytic machine, which degrades most intracellular proteins. We found that thioredoxin, Txnl1/TRP32, binds to Rpn11, a subunit of the regulatory complex of the human 26 S proteasome. Txnl1 is abundant, metabolically stable, and widely expressed and is present in the cytoplasm and nucleus. Txnl1 has thioredoxin activity with a redox potential of about -250 mV. Mutant Txnl1 with one active site cysteine replaced by serine formed disulfide bonds to eEF1A1, a substrate-recruiting factor of the 26 S proteasome. eEF1A1 is therefore a likely physiological substrate. In response to knockdown of Txnl1, ubiquitin-protein conjugates were moderately stabilized. Hence, Txnl1 is the first example of a direct connection between protein reduction and proteolysis, two major intracellular protein quality control mechanisms.
Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark.
Katrine M
KM
Andersen
Louise
L
Madsen
Søren
S
Prag
Anders H
AH
Johnsen
Colin A
CA
Semple
Klavs B
KB
Hendil
Rasmus
R
Hartmann-Petersen
D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D020648:Peptide Elongation Factor 1 / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D012995:Solubility; D013379:Substrate Specificity; D013879:Thioredoxins / Q000737:chemistry / Q000378:metabolism*
C094814:EEF1A1 protein, human; D020648:Peptide Elongation Factor 1; C504766:TXNL1 protein, human; D013879:Thioredoxins; D046988:Proteasome Endopeptidase Complex; C119011:26S proteasome non-ATPase regulatory subunit 13