Thioredoxin Txnl1/TRP32 Is a Redox-active Cofactor of the 26 S Proteasome

Katrine M Andersen; Louise Kjær Klausen; Søren Prag; Anders H Johnsen; Colin A Semple; Klavs B Hendil; Rasmus Hartmann-Petersen

doi:10.1074/jbc.M900016200

Thioredoxin Txnl1/TRP32 Is a Redox-active Cofactor of the 26 S Proteasome

Katrine M Andersen, Louise Kjær Klausen, Søren Prag, Anders H Johnsen, Colin A Semple, Klavs B Hendil, Rasmus Hartmann-Petersen

Biomolecular Sciences

55 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Biological Chemistry
Volume	284
Issue number	22
Pages (from-to)	15246-15254
ISSN	0021-9258
DOIs	https://doi.org/10.1074/jbc.M900016200
Publication status	Published - 2009

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title = "Thioredoxin Txnl1/TRP32 Is a Redox-active Cofactor of the 26 S Proteasome",

abstract = "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.",

author = "Andersen, {Katrine M} and Klausen, {Louise Kj{\ae}r} and S{\o}ren Prag and Johnsen, {Anders H} and Semple, {Colin A} and Hendil, {Klavs B} and Rasmus Hartmann-Petersen",

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doi = "10.1074/jbc.M900016200",

language = "English",

volume = "284",

pages = "15246--15254",

journal = "Journal of Biological Chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology, Inc.",

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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 -

Thioredoxin Txnl1/TRP32 Is a Redox-active Cofactor of the 26 S Proteasome

Abstract

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