Skip to Content
Merck
  • The conserved Trp114 residue of thioredoxin reductase 1 has a redox sensor-like function triggering oligomerization and crosslinking upon oxidative stress related to cell death.

The conserved Trp114 residue of thioredoxin reductase 1 has a redox sensor-like function triggering oligomerization and crosslinking upon oxidative stress related to cell death.

Cell death & disease (2015-01-23)
J Xu, S E Eriksson, M Cebula, T Sandalova, E Hedström, I Pader, Q Cheng, C R Myers, W E Antholine, P Nagy, U Hellman, G Selivanova, Y Lindqvist, E S J Arnér
ABSTRACT

The selenoprotein thioredoxin reductase 1 (TrxR1) has several key roles in cellular redox systems and reductive pathways. Here we discovered that an evolutionarily conserved and surface-exposed tryptophan residue of the enzyme (Trp114) is excessively reactive to oxidation and exerts regulatory functions. The results indicate that it serves as an electron relay communicating with the FAD moiety of the enzyme, and, when oxidized, it facilitates oligomerization of TrxR1 into tetramers and higher multimers of dimers. A covalent link can also be formed between two oxidized Trp114 residues of two subunits from two separate TrxR1 dimers, as found both in cell extracts and in a crystal structure of tetrameric TrxR1. Formation of covalently linked TrxR1 subunits became exaggerated in cells on treatment with the pro-oxidant p53-reactivating anticancer compound RITA, in direct correlation with triggering of a cell death that could be prevented by antioxidant treatment. These results collectively suggest that Trp114 of TrxR1 serves a function reminiscent of an irreversible sensor for excessive oxidation, thereby presenting a previously unrecognized level of regulation of TrxR1 function in relation to cellular redox state and cell death induction.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
α-Cyano-4-hydroxycinnamic acid, 97%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Acetonitrile, anhydrous, 99.8%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
α-Cyano-4-hydroxycinnamic acid, 99%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
1,6-Hexanediol, 99%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
SKU
Pack Size
Availability
Price
Quantity
Supelco
Acetonitrile, analytical standard
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hexylene glycol, BioXtra, ≥99% (GC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hexylene glycol, 99%
SKU
Pack Size
Availability
Price
Quantity
Supelco
α-Cyano-4-hydroxycinnamic acid, matrix substance for MALDI-MS, ≥99.0% (HPLC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Ammonium bicarbonate, BioUltra, ≥99.5% (T)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hexylene glycol, BioUltra, ≥99.0% (GC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hexylene glycol, puriss., ≥99.0% (GC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
α-Cyano-4-hydroxycinnamic acid, suitable for MALDI-TOF MS
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
SKU
Pack Size
Availability
Price
Quantity
Supelco
Dimethyl sulfoxide, analytical standard
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Phenylacetic acid, 99%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Phenylacetic acid, ≥99%, FCC, FG
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
1,6-Hexanediol, 97%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
SKU
Pack Size
Availability
Price
Quantity
USP
Residual Solvent Class 2 - Acetonitrile, United States Pharmacopeia (USP) Reference Standard
SKU
Pack Size
Availability
Price
Quantity
SAFC
Hexylene glycol
SKU
Pack Size
Availability
Price
Quantity
Dimethyl sulfoxide, European Pharmacopoeia (EP) Reference Standard
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Ultrapure Acetonitrile
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Acetonitrile, electronic grade, 99.999% trace metals basis
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
α-Cyano-4-hydroxycinnamic acid, matrix substance for MALDI-MS, Ultra pure
SKU
Pack Size
Availability
Price
Quantity
Supelco
Dimethyl sulfoxide, for inorganic trace analysis, ≥99.99995% (metals basis)
SKU
Pack Size
Availability
Price
Quantity
USP
Dimethyl sulfoxide, United States Pharmacopeia (USP) Reference Standard
SKU
Pack Size
Availability
Price
Quantity
Supelco
Acetonitrile, Pharmaceutical Secondary Standard; Certified Reference Material
SKU
Pack Size
Availability
Price
Quantity