The A to Z of modulated cell patterning by mammalian thioredoxin reductases.
The A to Z of modulated cell patterning by mammalian thioredoxin reductases.
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哺乳动物硫氧还蛋白还原酶调节细胞模式的 A 到 Z。
DOI：
10.1016/j.freeradbiomed.2017.12.029
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发表时间：
2018-02-01
影响因子：
7.4
通讯作者：
Arnér ESJ
中科院分区：
文献类型：
--
作者：
Dagnell M;Schmidt EE;Arnér ESJ
哺乳动物硫氧还蛋白还原酶 (TrxRs) 是含硒代半胱氨酸的蛋白质（硒蛋白），通过还原包括硫氧还蛋白 (Trxs) 活性位点二硫化物在内的多种底物来推动大量功能。 Trxs 和 TrxRs 支持的众所周知的酶系统包括通过核糖核苷酸还原酶的脱氧核糖核苷酸合成、通过过氧化氧还蛋白和甲硫氨酸亚砜还原酶的抗氧化防御以及许多转录因子的氧化还原调节。尽管这些功能对于细胞来说可能是必需的，因为它们在维持细胞活力和增殖方面发挥着至关重要的作用，但过去十年的研究结果表明，哺乳动物的细胞还原系统存在大量冗余。谷胱甘肽 (GSH) 的合成和 GSH 依赖性途径的还原功能通常与 Trx 依赖性途径并行作用，通常只有这些系统之一足以支持活力。重要的是，这并不意味着 Trx 系统的调节不会产生任何后果，即使 GSH 依赖性途径仍然发挥作用。正如最近的几项研究结果表明，一般而言 Trx 系统，特别是 TrxR，是信号通路的关键调节因子。在这篇综述文章中，我们将讨论这些发现，这些发现共同表明哺乳动物细胞质 TrxR1 (TXNRD1) 或线粒体 TrxR2 (TXNRD2) 系统的调节会影响细胞模式和细胞应激反应。较低活动的影响包括脂肪生成增加、胰岛素反应性、糖原积累、过度增殖和胚胎发育扭曲，而活动增加则与增殖减少、寿命延长以及癌症预后较差相关。将讨论这些不同作用背后的分子机制，包括蛋白质磷酸化级联的调节和指导细胞分化途径的关键转录因子。我们的结论是，硒依赖性氧化还原酶 TrxR1 和 TrxR2 应被视为控制细胞分化和细胞应激反应的信号通路的关键组成部分。
Mammalian thioredoxin reductases (TrxRs) are selenocysteine-containing proteins (selenoproteins) that propel a large number of functions through reduction of several substrates including the active site disulfide of thioredoxins (Trxs). Well-known enzymatic systems that in turn are supported by Trxs and TrxRs include deoxyribonucleotide synthesis through ribonucleotide reductase, antioxidant defense through peroxiredoxins and methionine sulfoxide reductases, and redox modulation of a number of transcription factors. Although these functions may be essential for cells due to crucial roles in maintenance of cell viability and proliferation, findings during the last decade reveal that mammals have major redundancy in their cellular reductive systems. The synthesis of glutathione (GSH) and reductive functions of GSH-dependent pathways typically act in parallel with Trx-dependent pathways, with only one of these systems often being sufficient to support viability. Importantly, this does not imply that a modulation of the Trx system will remain without consequences, even when GSH-dependent pathways remain functional. As suggested by several recent findings, the Trx system in general and the TrxRs in particular, function as key regulators of signaling pathways. In this review article we will discuss findings that collectively suggest that modulation in mammalian systems of cytosolic TrxR1 (TXNRD1) or mitochondrial TrxR2 (TXNRD2) influence cell patterning and cellular stress responses. Effects of lower activities include increased adipogenesis, insulin responsiveness, glycogen accumulation, hyperproliferation, and distorted embryonic development, while increased activities correlate with decreased proliferation and extended lifespan, as well as worse cancer prognosis. The molecular mechanisms that underlie these diverse effects, involving regulation of protein phosphorylation cascades and of key transcription factors that guide cellular differentiation pathways, will be discussed. We conclude that the selenium-dependent oxidoreductases TrxR1 and TrxR2 should be considered as key components of signaling pathways that control cell differentiation and cellular stress responses.
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影响因子：
3.7
作者：
Anestål K;Prast-Nielsen S;Cenas N;Arnér ES
通讯作者：
Arnér ES
乳腺癌细胞入侵和迁移中的硫氧还蛋白系统。
影响因子：
11.4
作者：
Bhatia M;McGrath KL;Di Trapani G;Charoentong P;Shah F;King MM;Clarke FM;Tonissen KF
通讯作者：
Tonissen KF
影响因子：
5.3
作者：
Conrad, M;Jakupoglu, C;Brielmeier, M
通讯作者：
Brielmeier, M
影响因子：
64.5
作者：
Chio IIC;Jafarnejad SM;Ponz-Sarvise M;Park Y;Rivera K;Palm W;Wilson J;Sangar V;Hao Y;Öhlund D;Wright K;Filippini D;Lee EJ;Da Silva B;Schoepfer C;Wilkinson JE;Buscaglia JM;DeNicola GM;Tiriac H;Hammell M;Crawford HC;Schmidt EE;Thompson CB;Pappin DJ;Sonenberg N;Tuveson DA
通讯作者：
Tuveson DA
DOI：
10.1186/bcr2599
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Cadenas C;Franckenstein D;Schmidt M;Gehrmann M;Hermes M;Geppert B;Schormann W;Maccoux LJ;Schug M;Schumann A;Wilhelm C;Freis E;Ickstadt K;Rahnenführer J;Baumbach JI;Sickmann A;Hengstler JG
通讯作者：
Hengstler JG