Thioredoxin Regulates Cell Cycleviathe ERK1/2-Cyclin D1 Pathway

Abstract

Thioredoxin (TRX) is a key component of redox regulation and has been indicated to play an essential role in cell survival and growth. Here, we investigated the molecular mechanism of TRX in the regulation of cell survival and growth by using RNA interference (RNAi) in A549 lung cancer and MCF7 breast cancer cells. TRX knockdown did not significantly increase the basal level of cell death without exposure to stress, but CDDP-induced cell death was enhanced. Meanwhile, TRX knockdown resulted in significant cell-cycle arrest at the G(1) phase. Cyclin D1 expression was reduced by TRX knockdown at the protein and mRNA levels. TRX knockdown caused suppression of activation of the cyclin D1 promoter through elements including AP-1. TRX knockdown also reduced the levels of phosphorylated ERK1/2 and the nuclear translocation of ERK 1/2 induced by EGF. These results suggest that TRX is an important regulator of the cell cycle in the G(1) phase via cyclin D1 transcription and the ERK/AP-1 signaling pathways.

Thioredoxin interacting protein (TXNIP) rs7212 polymorphism is associated with arterial stiffness in the Brazilian general population

“…4,10 Based on this, we suggest that TXNIP rs7212 polymorphism may be associated with significant changes in the vascular bed due to an increased reactive oxygen species production, which are widely associated with diabetes and known to lead to increased arterial stiffness.…”

Thioredoxin-like protein 2b facilitates colon cancer cell proliferation and inhibits apoptosis via NF-κB pathway

“…However, there are still many unsettled questions concerning the function of Txl-2. Because expression of Trx family members is frequently associated with aggressive tumor growth, resistance to standard chemotherapy and decreased patient survival [21,25], we wondered whether it affected colon cancer cell growth and anti-apoptotic function. In the current study, through an immunohistochemical study, we determined that overexpressed Txl-2 was significantly correlated with tumor staging and cancer cell differentiation, suggesting that Txl-2 might be involved in the regulation of tumor progression.…”

Activation of the phosphatidylinositol 3′-kinase/AKT pathway in neuroblastoma and its regulation by thioredoxin 1

“…TRX-transgenic mice are more resistant to infection, inflammation, and ischemic diseases and survive longer than control mice [39]. TRX is an important regulator of the cell cycle in the G 1 phase via cyclin D1 transcription and the ERK/AP-1 (extracellular signal-regulated kinase/ activator protein-1) signaling pathways [40]. However, TRX-1 was found to bind to the catalytic site of PTEN and to its C2 lipid membrane-binding domain [22].…”