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Figure 1 | Breast Cancer Research

Figure 1

From: Role of thioredoxin reductase 1 and thioredoxin interacting protein in prognosis of breast cancer

Figure 1

Scheme of cellular functions of the cytoplasmic thioredoxin system. Thioredoxin reductase 1 (TXNRD1) reduces thioredoxin 1 (TXN), which in turn reduces oxidized cysteins in cellular proteins and scavenges peroxides by peroxiredoxins (PRDX), thus protecting cells against oxidative stress. TXN stimulates ribonucleotide reductase (RR) activity and supports DNA synthesis. TXN stimulates the transcriptional activity of nuclear factor κB (NF-κB), activator protein 1 (Fos/Jun) (AP-1) and specificity protein 1 (SP-1), and elevates hypoxia inducible factor 1α (HIF-1α) protein levels, which in turn influence vascular endothelial growth factor (VEGF). TXN also binds to and inhibits the pro-apoptotic proteins apoptosis signal regulating kinase 1 (ASK-1) and phosphatase and tensin homolog (PTEN). All these events promote cell growth, inhibit apoptosis and increase angiogenesis in tumors, as reviewed elsewhere [8]. Thioredoxin interacting protein (TXNIP) binds and inhibits reduced TXN. TXNIP also interacts with several transcriptional co-repressors, such as promyelocytic leukemia zinc-finger (PLZF), Fanconi anemia zinc-finger (FAZF) and histone deacetylase 1 (HDAC1), and inhibits transcription of cyclin A2, leading to reduced cell growth. TXNIP increases p16 and p27KIP1 protein levels, leading to cell cycle arrest. TXNIP also associates with the von Hippel-Landau protein (pVHL), enhancing the interaction between pVHL and HIF1α to promote nuclear export and degradation of HIF1α. The roles of TXNIP in the immune system and in human metabolism are not yet fully understood. For reviews, see [13, 14]. CDK, cycline dependent kinase; FA, fatty acid; ROS, reactive oxygen species.

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