Thioredoxin-1 (TRX1) (TRX1)

Thioredoxin-1 (TRX1) is a small, 12-kDa multifunctional protein that serves as a primary antioxidant and a key regulator of cellular redox homeostasis [UniProt P10599]. It functions as a disulfide reductase, utilizing a conserved Cys-Gly-Pro-Cys active site to reduce oxidized cysteine residues in target proteins, a process fueled by NADPH and thioredoxin reductase [PMID: 17569118]. TRX1 is frequently overexpressed in various malignancies, where it promotes tumor growth, angiogenesis, and resistance to apoptosis by modulating signaling pathways such as NF-kappaB and scavenging reactive oxygen species [PMID: 22133856]. In the cytoplasm, TRX1 primarily manages oxidative stress, while in the nucleus, it interacts with transcription factors like p53 and AP-1 to regulate gene expression [PMID: 10642553]. Because of its central role in cancer cell survival and its correlation with poor prognosis, TRX1 is a prominent target for small-molecule inhibitors like PX-12 [PMID: 15059912]. Additionally, TRX1's involvement in inflammatory and cardiovascular conditions makes it a subject of interest for broader therapeutic applications beyond oncology [PMID: 28254964].

Other names

TXN [NCBI Gene: 7295]TRXTRDXAdult T-cell leukemia-derived factor (ADF)Surface-associated sulfhydryl protein (SASP)

Inhibition of the thioredoxin system, typically by irreversibly binding to the active site cysteine residues (Cys32/Cys35) of TRX1 or by inhibiting the regenerating enzyme thioredoxin reductase (TrxR), which leads to increased intracellular reactive oxygen species (ROS), oxidative stress, and the induction of apoptosis [PMID: 28254964].