TY - JOUR
T1 - Thioredoxin Txnl1/TRP32 Is a Redox-active Cofactor of the 26 S Proteasome
AU - Andersen, Katrine M.
AU - Madsen, Louise
AU - Prag, Soren
AU - Johnsen, Anders H.
AU - Semple, Colin A.
AU - Hendil, Klavs B.
AU - Hartmann-Petersen, Rasmus
PY - 2009/5/29
Y1 - 2009/5/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=67649359951&partnerID=8YFLogxK
U2 - 10.1074/jbc.M900016200
DO - 10.1074/jbc.M900016200
M3 - Article
C2 - 19349277
SN - 0021-9258
VL - 284
SP - 15246
EP - 15254
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 22
ER -