Possible association of thioredoxin and p53 in breast cancer

Ueno, Masaya; Matsutani, Yasuo; Nakamura, Hajime; Masutani, Hiroshi; Yagi, Michio; Yamashiro, Hiroyasu; Kato, Hironori; Inamoto, Takashi; Yamauchi, Akira; Takahashi, Rei; Yamaoka, Yoshio; Yodoi, Junji

doi:10.1016/s0165-2478(00)00284-4

Cited by 24 publications

(15 citation statements)

References 22 publications

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“…Ref-1 was found to be an activity of a DNA repair enzyme apurinic/apyrimidinic endonuclease [41]. Subsequent studies showed that similar nuclear redox control mechanisms function for NF-κB, Nrf-2, GR, estrogen receptor, p53 and HIF-1α [6], [8], [13], [16], [17], [42]. Importantly, Hirota et al found that cytoplasmic Trx1 suppressed NF-κB activation by UV irradiation, whereas targeted expression of Trx1 in nuclei enhanced NF-κB activity by increasing DNA binding [5].…”

Section: Discussionmentioning

confidence: 99%

“…Although little is known about the adaptive mechanisms for the nuclear GSH system, the function of the nuclear Trx1 system is enhanced by translocation of Trx1 from cytoplasm to nuclei. This translocation is critical to function of transcription factors that contain a regulatory cysteine in the DNA binding region, including nuclear factor-κB (NF-κB) [4], [5], [6], glucocorticoid receptor (GR) [7], [8], activator protein-1 [9], [10], [11], nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) [12], [13], Hypoxia-inducible factor 1 alpha (HIF-1α) [14] and p53 [15], [16].…”

Section: Introductionmentioning

confidence: 99%

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Increased Inflammatory Signaling and Lethality of Influenza H1N1 by Nuclear Thioredoxin-1

Kang

Roede

et al. 2011

PLoS ONE

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BackgroundCell culture studies show that the antioxidant thiol protein, thioredoxin-1 (Trx1), translocates to cell nuclei during stress, facilitates DNA binding of transcription factors NF-κB and glucocorticoid receptor (GR) and potentiates signaling in immune cells. Excessive proinflammatory signaling in vivo contributes to immune hyper-responsiveness and disease severity, but no studies have addressed whether nuclear Trx1 mediates such responses.Methodology/Principal FindingsTransgenic mice (Tg) expressing human Trx1 (hTrx1) with added nuclear localization signal (NLS) showed broad tissue expression and nuclear localization. The role of nuclear Trx1 in inflammatory signaling was examined in Tg and wild-type (WT) mice following infection with influenza (H1N1) virus. Results showed that Tg mice had earlier and more extensive NF-κB activation, increased TNF-α and IL-6 expression, greater weight loss, slower recovery and increased mortality compared to WT. Decreased plasma glutathione (GSH) and oxidized plasma GSH/GSSG redox potential (EhGSSG) following infection in Tg mice showed that the increased nuclear thiol antioxidant caused a paradoxical downstream oxidative stress. An independent test of this nuclear reductive stress showed that glucocorticoid-induced thymocyte apoptosis was increased by NLS-Trx1.Conclusion/SignificanceIncreased Trx1 in cell nuclei can increase severity of disease responses by potentiation of redox-sensitive transcription factor activation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased Inflammatory Signaling and Lethality of Influenza H1N1 by Nuclear Thioredoxin-1

Kang

Roede

et al. 2011

PLoS ONE

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“…The protective effects of selenium against cancer development (21) may therefore possibly be linked to the ref-1-dependent selenomethionine-induced maturation of p53 as a DNA repair enzyme (98). For this to occur, selenomethionine may possibly lead to an increased activity or synthesis of TrxR1, subsequently leading to an increased ref-1-dependent modulation of p53 by Trx (74,112,113).…”

Section: Trxr1 Regulation and Function In Relation To Cancermentioning

confidence: 99%

Regulation of the Mammalian Selenoprotein Thioredoxin Reductase 1 in Relation to Cellular Phenotype, Growth, and Signaling Events

Rundlöf

Arnér

2004

Antioxidants & Redox Signaling

176

125

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Reactive oxygen species (ROS) are generated as toxic by-products of aerobic metabolism, but are also essential biomolecules in cell signaling. The thioredoxin (Trx) system is a major enzymatic system modulating ROS levels and is important for redox regulation of cellular function. It consists of Trx and thioredoxin reductase (TrxR), which reduces Trx using NADPH. Most, if not all, of the functions of Trx depend on the activity of TrxR. Mammalian TrxR enzymes are selenoproteins with broad substrate specificities, and alteration of cytosolic TrxR1 expression and activity is likely to be an important determinant for the control of cellular redox regulation. TrxR1 activity in cells seems to be modulated by an intricate interplay, involving a housekeeping type promoter in combination with alternative splice variants and transcriptional start sites, posttranscriptional regulation through AU-rich elements, inactivation by electrophilic agents and by itself modulating the effects of several key signaling molecules. TrxR1 activity is also intimately linked with several aspects of selenium metabolism, and hence selenoprotein function in general. Here, we summarize the current knowledge of these different levels of TrxR1 regulation in diverse cell types and in response to growth and signaling events.

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“…Through these substrates, Trx1 plays important roles in DNA synthesis and cellular redox maintaining. In addition, Trx1 is also known to regulate several transcription factors such as NF-κB, p53 and Ref-1, as well as some apoptosis factors like apoptosis signal-regulating kinase 1 (ASK1) [12][13][14][15][16]. Trx1 redox state and TrxR1 activity are crucial factors for cell fate, especially for cancer cells since Trx1 and TrxR1 are overexpressed to balance the elevated reactive oxygen species (ROS) in many cancer cells [12,14,16,17].…”

Section: Introductionmentioning

confidence: 99%

Oxidation of structural cysteine residues in thioredoxin 1 by aromatic arsenicals enhances cancer cell cytotoxicity caused by the inhibition of thioredoxin reductase 1

Zhang

Ren

et al. 2015

Free Radical Biology and Medicine

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Possible association of thioredoxin and p53 in breast cancer

Cited by 24 publications

References 22 publications

Increased Inflammatory Signaling and Lethality of Influenza H1N1 by Nuclear Thioredoxin-1

Increased Inflammatory Signaling and Lethality of Influenza H1N1 by Nuclear Thioredoxin-1

Regulation of the Mammalian Selenoprotein Thioredoxin Reductase 1 in Relation to Cellular Phenotype, Growth, and Signaling Events

Oxidation of structural cysteine residues in thioredoxin 1 by aromatic arsenicals enhances cancer cell cytotoxicity caused by the inhibition of thioredoxin reductase 1

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