Thioredoxin-interacting protein (txnip) is a glucocorticoid-regulated primary response gene involved in mediating glucocorticoid-induced apoptosis

Wang, Z; Rong, Yiping; Malone, Michael H.; Davis, Michael C.; Zhong, Fei; Distelhorst, Clark W.

doi:10.1038/sj.onc.1209218

Cited by 102 publications

(97 citation statements)

References 46 publications

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“…Interestingly, the gene expression signature generated following MondoA knockdown showed significant overlap with a gene signature that portended a good prognosis for B-ALL patients treated with glucocorticoids (Rhein et al 2007). This finding contrasts with other reports indicating that TXNIP contributes to glucocorticoid-driven apoptosis in a number of T-cell leukemia cell lines (Wang et al 2006;Chen et al 2010b). It may be that in B-ALL, MondoA cannot regulate TXNIP and this tumor/growthsuppressive axis is not intact.…”

Section: Max-and Mlx-centered Transcription Networkcontrasting

confidence: 56%

Coordination of Nutrient Availability and Utilization by MAX- and MLX-Centered Transcription Networks

O’Shea

Ayer

2013

Cold Spring Harbor Perspectives in Medicine

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Cell growth and division require the biosynthesis of macromolecule components and cofactors (e.g., nucleotides, lipids, amino acids, and nicotinamide adenine dinucleotide phosphate [NADPH]). Normally, macromolecular biosynthesis is under tight regulatory control, yet these anabolic pathways are often dysregulated in cancer. The resulting metabolic reprogramming of cancer cells is thought to support their high rates of growth and division. The mechanisms that underlie the metabolic changes in cancer are at least partially understood, providing a rationale for their targeting with known or novel therapeutics. This review is focused on how cells sense and respond transcriptionally to essential nutrients, including glucose and glutamine, and how MAX-and MLX-centered transcription networks contribute to metabolic homeostasis in normal and neoplastic cells.

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Section: Max-and Mlx-centered Transcription Networkcontrasting

confidence: 56%

Coordination of Nutrient Availability and Utilization by MAX- and MLX-Centered Transcription Networks

O’Shea

Ayer

2013

Cold Spring Harbor Perspectives in Medicine

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“…Bcl-2-positive cells were transiently transfected by electroporation with the pEGFP-C1-LC3 plasmid, kindly provided by Tamotsu Yoshimori and Noboru Mizushima 15 using previously described electroporation conditions. 44 After incubation for 1 hr, 1 μM Dex was added to the cells which were then incubated in poly-L-lysine coated MatTek cultureware plates for 1 hr at 37°C, allowing the cells to adhere. Images were taken using an inverted Leica DMI 6000 fluorescence microscope, equipped with an environmental chamber set at 37°C and 7% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Apoptosis inhibition by Bcl-2 gives way to autophagy in glucocorticoid-treated lymphocytes

et al. 2008

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Glucocorticosteroid hormones, including prednisone and dexamethasone (Dex), have been used to treat lymphoid malignancies for many years because they readily induce apoptosis in immature lymphocytes lacking Bcl-2. However, elevated expression of the anti-apoptotic protein Bcl-2 inhibits apoptosis and contributes to glucocorticoid resistance. Using the Bcl-2-negative WEHI7.2 lymphoma line as an experimental model, we found that Dex not only induces apoptosis but also induces autophagy. The caspase inhibitor Z-VAD-fmk inhibited apoptosis but not autophagy in Dex-treated cells. Bcl-2 overexpression inhibited Dex-induced apoptosis even more potently than Z-VAD-fmk and, contrary to previous reports, Bcl-2 neither interacted with Beclin-1 nor inhibited autophagy. Rather, Bcl-2 overexpression facilitated detection of Dex-induced autophagy by both steady state methods and flux measurements, ostensibly due to apoptosis inhibition. Autophagy contributed to prolonged survival of Bcl-2-positive lymphoma cells following Dex treatment, as survival was reduced when autophagy was inhibited by 3-methyladenine. These findings emphasize the important interplay between apoptosis and autophagy and suggest a novel mechanism by which Bcl-2, which is frequently elevated in lymphoid malignancies, contributes to glucocorticoid resistance and survival of lymphoma cells.

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“…In many cancer cell lines or cancer tissues, the expression of the Txnip gene is down-regulated; because Txnip can inhibit cell proliferation and promote apoptosis, it is thought that low Txnip expression may contribute to cancer development (2)(3)(4)(5)(6)(7)(8). Recently, Txnip was identified as a negative regulator for cellular glucose uptake (9 -11); Txnip knockout mice exhibit abnormalities in glucose and lipid metabolism (4,(12)(13)(14).…”

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confidence: 99%

Thioredoxin-interacting Protein (Txnip) Gene Expression

Chai

et al. 2010

Journal of Biological Chemistry

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Thioredoxin-interacting protein (Txnip) has important functions in regulating cellular metabolism including glucose utilization; the expression of the Txnip gene is sensitive to the availability of glucose and other fuels. Here, we show that Txnip expression is down-regulated at the transcriptional level by diverse inhibitors of mitochondrial oxidative phosphorylation (OXPHOS). The effect of these OXPHOS inhibitors is mediated by earlier identified carbohydrate-response elements (ChoREs) on the Txnip promoter and the ChoRE-associated transcription factors Max-like protein X (MLX) and MondoA (or carbohydrate-response element-binding protein (ChREBP)) involved in glucose-induced Txnip expression, suggesting that inhibited oxidative phosphorylation compromises glucose-induced effects on Txnip expression. We also show that the OXPHOS inhibitors repress the Txnip transcription most likely by inducing the glycolytic rate, and increased glycolytic flux decreases the levels of glycolytic intermediates important for the function of MLX and MondoA (or ChREBP). Our findings suggest that the Txnip expression is tightly correlated with glycolytic flux, which is regulated by oxidative phosphorylation status. The identified link between the Txnip expression and glycolytic activityimpliesamechanismbywhichthecellularglucoseuptake/ homeostasis is regulated in response to various metabolic cues, oxidative phosphorylation status, and other physiological signals, and this may facilitate our efforts toward understanding metabolism in normal or cancer cells. Thioredoxin-interacting-protein (Txnip)3 plays important roles in diverse physiological or pathological processes (reviewed in Ref 1). In many cancer cell lines or cancer tissues, the expression of the Txnip gene is down-regulated; because Txnip can inhibit cell proliferation and promote apoptosis, it is thought that low Txnip expression may contribute to cancer development (2-8). Recently, Txnip was identified as a negative regulator for cellular glucose uptake (9 -11); Txnip knockout mice exhibit abnormalities in glucose and lipid metabolism (4,(12)(13)(14). These observations are in line with critical function(s) of Txnip in metabolic control.The expression of the Txnip gene is sensitive to many nutritional factors. Txnip was originally identified as a vitamin D up-regulated protein (VDUP1 (15)), and the Txnip expression was later shown to be induced by glucose, which is mediated by carbohydrate-response elements (ChoREs (16 -18)) and associated transcription factors Max-like protein X (MLX) and Mondo (MondoA or ChoRE-binding protein (ChREBP, which is also dubbed as MondoB) (18 -20)). Moreover, the Txnip expression is modulated by glutamine, potentially through glutaminolysis, fatty acids, and an array of adenosine-containing molecules (21-23). The capability of the Txnip gene to sense diverse nutrients and to regulate their utilization implies a mechanism for cells to integrate different signaling pathways evoked by diverse nutritional factors.In the current study, we wished t...

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Thioredoxin-interacting protein (txnip) is a glucocorticoid-regulated primary response gene involved in mediating glucocorticoid-induced apoptosis

Cited by 102 publications

References 46 publications

Coordination of Nutrient Availability and Utilization by MAX- and MLX-Centered Transcription Networks

Coordination of Nutrient Availability and Utilization by MAX- and MLX-Centered Transcription Networks

Apoptosis inhibition by Bcl-2 gives way to autophagy in glucocorticoid-treated lymphocytes

Thioredoxin-interacting Protein (Txnip) Gene Expression

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