Thioredoxin-related protein of 14 kDa as a modulator of redox signalling pathways.

Thioredoxin-related protein of 14 kDa (TRP14; also named TXNDC17 for thioredoxin domain-containing protein 17) is a highly conserved and ubiquitously expressed oxidoreductase. It is expressed in parallel with thioredoxin 1 (Trx1, TXN; TXN1), an efficient substrate for the mammalian cytosolic selenoprotein thioredoxin reductase 1 (TrxR1; TXNRD1). However, TRP14, in sharp contrast to Trx1, cannot support the activities of ribonucleotide reductase, peroxiredoxins or methionine sulfoxide reductases, thus is unable to directly support cell proliferation or antioxidant defence through these pathways. However, TRP14 has been shown to efficiently reduce l-cystine, which thereby indirectly supports glutathione synthesis. TRP14 can also suppress NF-κB signalling, is functionally linked to STAT3 signalling, and can directly reactivate oxidized protein-tyrosine phosphatase PTP1B. Furthermore, TRP14 can efficiently reduce persulfidated or nitrosylated cysteine residues in many proteins, thereby having the capacity to modulate signalling through hydrogen sulfide or NO. Additional bioinformatics analyses and observations suggest further roles for TRP14; therefore, further studies of its functions are warranted. Collectively, the results available suggest that TRP14 is a member of the thioredoxin system dedicated to the control of cellular redox signalling pathways. LINKED ARTICLES: This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc.