Trx1

Trx1, or thioredoxin-1, is a small, highly conserved redox protein that helps maintain cellular redox homeostasis. In humans it is a ~12 kDa cytosolic protein that participates in thiol-disulfide exchange and regulates the redox state of target proteins.

It operates as part of the thioredoxin system by catalyzing thiol-disulfide exchange reactions, reducing disulfide bonds in substrates and thereby modulating their structure and activity. Trx1 contains an active site motif Cys-Gly-Pro-Cys essential for catalysis. Recycling of Trx1 from its oxidized form is mediated by thioredoxin reductase (TrxR) and NADPH. Through these actions, Trx1 participates in DNA synthesis via ribonucleotide reductase and modulates transcription factors such as NF-kB and AP-1, as well as the activity of antioxidant enzymes like peroxiredoxins.

Localization and regulation: Trx1 is predominantly cytosolic and nuclear in most cells, and can be secreted under stress, where extracellular Trx1 can act as a cytokine-like mediator in inflammation. In humans, Trx1 is encoded by the TXN gene. Expression is constitutive but upregulated by oxidative stress and inflammatory signals; the redox state of Trx1 often determines its activity.

Clinical significance: Trx1 is implicated in cancer, cardiovascular diseases, inflammatory conditions, and aging. Elevated Trx1 levels have been observed in several cancers and inflammatory states, and the thioredoxin system is a target for therapy. Inhibitors of Trx1 or its reductase, such as PX-12 and auranofin, have been explored in preclinical and clinical contexts.