TY - JOUR
T1 - Thioredoxin Txnl1/TRP32 Is a Redox-active Cofactor of the 26 S Proteasome
AU - Andersen, Katrine M
AU - Klausen, Louise Kjær
AU - Prag, Søren
AU - Johnsen, Anders H
AU - Semple, Colin A
AU - Hendil, Klavs B
AU - Hartmann-Petersen, Rasmus
PY - 2009
Y1 - 2009
N2 - The 26S 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 26S 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 26S proteasome. eEF1A1 is therefore a likely physiological substrate. In response to knock-down of Txnl1, ubiquitin-protein conjugates were moderately stabilised. Hence, Txnl1 is the first example of a direct connection between protein reduction and proteolysis, two major intracellular protein quality control mechanisms.
AB - The 26S 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 26S 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 26S proteasome. eEF1A1 is therefore a likely physiological substrate. In response to knock-down of Txnl1, ubiquitin-protein conjugates were moderately stabilised. Hence, Txnl1 is the first example of a direct connection between protein reduction and proteolysis, two major intracellular protein quality control mechanisms.
U2 - 10.1074/jbc.M900016200
DO - 10.1074/jbc.M900016200
M3 - Journal 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 -