Hydrogen peroxide sensing, signaling and regulation of transcription factors.
Hydrogen peroxide sensing, signaling and regulation of transcription factors.
复制标题
DOI：
10.1016/j.redox.2014.02.006
复制
发表时间：
2014
期刊：
影响因子：
11.4
通讯作者：
Antunes F
中科院分区：
文献类型：
--
作者：
Marinho HS;Real C;Cyrne L;Soares H;Antunes F
综述了过氧化氢（H2O2）对细菌（OxyR和PerR）、低等真核生物（Yap 1、Maf 1、Hsf1和Msn2/4）和哺乳动物细胞（AP-1、NRF 2、CREB、HSF 1、HIF-1、TP 53、NF-κ B、NOTCH、SP 1和SCRE B-1）中转录因子活性的调控机制。在整个系统发育树中，调控网络的复杂性增加，达到了很高的复杂性水平。多个H2O2传感器和途径在转录因子的调节中在几个水平上被触发会聚：（1）通过上调转录或增加mRNA稳定性和翻译来合成转录因子;（ii）通过减少转录因子与泛素E3连接酶复合物的结合或通过抑制该复合物来稳定转录因子;（iii）通过暴露/掩蔽核定位信号，或通过从配偶体或从膜锚释放转录因子来进行细胞质-核运输;和（iv）通过调节转录因子对DNA、共激活子或阻遏物的亲和力，并通过靶向染色质的特定区域来激活单个基因。我们还讨论了如何H2O2生物特异性的结果，从不同的巯基蛋白传感器，其巯基对H2O2的不同反应性，被激活不同的浓度和暴露于H2O2的时间。局部H2O2浓度的特定调节也是至关重要的，并且是由信号控制的H2O2局部产生和去除的结果。最后，我们制定方程，从典型的实验中提取定量数据H2O2与传感器分子的反应。估计H2O2与KEAP 1和介导NRF 2蛋白合成的未知靶点反应的速率常数分别为140 M − 1 s − 1和≥ 1.3 × 103 M − 1 s − 1。总之，众多的H2O2目标和机制提供了对基因调控的高度特异性影响的机会，这取决于细胞类型和从细胞微环境接收的信号。氧化还原调节的复杂性沿着系统发育树增加。复杂的调控网络允许高度的H2O2生物可塑性。H2O2在从转录到蛋白质合成的所有步骤中调节基因表达。快速响应由具有高H2O2反应性的传感器介导。低反应性H2O2传感器可介导缓慢（h）或局部H2O2响应。
The regulatory mechanisms by which hydrogen peroxide (H2O2) modulates the activity of transcription factors in bacteria (OxyR and PerR), lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4) and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1) are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1) synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii) stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii) cytoplasm–nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and (iv) DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M−1 s−1 and ≥1.3 × 103 M−1 s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for highly specific effects on gene regulation that depend on the cell type and on signals received from the cellular microenvironment. Complexity of redox regulation increases along the phylogenetic tree. Complex regulatory networks allow for a high degree of H2O2 biological plasticity. H2O2 modulates gene expression at all steps from transcription to protein synthesis. Fast response (s) is mediated by sensors with high H2O2 reactivity. Low reactivity H2O2 sensors may mediate slow (h) or localized H2O2 responses.
登录
查看更多内容
影响因子：
8
作者：
Bloom, D;Dhakshinamoorthy, S;Jaiswal, AK
通讯作者：
Jaiswal, AK
DOI：
10.1016/j.bbrc.2013.02.065
发表时间：
2013-03-29
影响因子：
3.1
作者：
Baird, Liam;Dinkova-Kostova, Albena T.
通讯作者：
Dinkova-Kostova, Albena T.
影响因子：
4.8
作者：
Bienert, Gerd P.;Moller, Anders L. B.;Jahn, Thomas P.
通讯作者：
Jahn, Thomas P.
影响因子：
--
作者：
Boisnard, Stephanie;Lagniel, Gilles;Chedin, Stephane
通讯作者：
Chedin, Stephane
影响因子：
16
作者：
Bossis, G;Melchior, F
通讯作者：
Melchior, F