TRAF family member-associated NF-kappa B activator (TANK) expression increases in injured sensory neurons and is transcriptionally regulated by Sox11.
TRAF family member-associated NF-kappa B activator (TANK) expression increases in injured sensory neurons and is transcriptionally regulated by Sox11.
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DOI：
10.1016/j.neuroscience.2012.11.034
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发表时间：
2013-02-12
期刊：
影响因子：
3.3
通讯作者：
Albers, K. M.
中科院分区：
文献类型：
--
作者：
Salerno, K. M.;Jing, X.;Diges, C. M.;Davis, B. M.;Albers, K. M.
周围神经损伤引起基因转录和细胞信号通路的快速和复杂的变化。了解这些变化是如何与功能相关的，对于开发加速和改善神经再生的新方法至关重要。为此，我们发现神经损伤诱导背根神经节（DRG）神经元中转录因子Sox11的快速和显著上调。功能的获得和丧失研究表明，这种增加对于正常的轴突再生是必不可少的。为了确定Sox11如何影响神经元基因表达，我们用Sox11 siRNA处理DRG神经元，以确定潜在的转录靶点。一个被Sox11敲除显著减少的基因是TRAF（肿瘤坏死因子（TNF）受体相关因子）-相关NF-κB激活因子（TANK）。本研究表明，TANK在DRG神经元中表达，周围神经损伤后，TANK表达增加，体外过表达Sox11会增加TANK表达。损伤和体外过表达也会优先增加TANK转录物变体3和更大的TANK蛋白异构体。为了确定Sox11是否调控TANK转录，我们使用生物信息学分析方法在多个哺乳动物基因组中，鉴定了TANK 5 '非翻译区（UTR） 5kbp内潜在的Sox结合基序。对小鼠TANK基因的两个位点进行了检测。荧光素酶表达试验结合定点诱变表明，每个位点都有助于增强TANK启动子活性。此外，染色质免疫沉淀试验显示，在小鼠TANK 5 ' -UTR中，含有两个已鉴定的Sox基序的区域直接结合了Sox11。这些研究首次表明，TANK在DRG神经元中表达，周围神经损伤会增加TANK的表达，并且对TANK表达的调节至少部分是由损伤相关转录因子Sox11控制的。
Peripheral nerve injury evokes rapid and complex changes in gene transcription and cellular signaling pathways. Understanding how these changes are functionally related is essential for developing new approaches that accelerate and improve nerve regeneration. Towards this goal we found that nerve injury induces a rapid and significant up-regulation of the transcription factor Sox11 in dorsal root ganglia (DRG) neurons. Gain and loss of function studies have shown this increase is essential for normal axon regeneration. To determine how Sox11 impacts neuronal gene expression, DRG neurons were treated with Sox11 siRNA to identify potential transcriptional targets. One gene significantly reduced by Sox11 knockdown was TRAF (tumor necrosis factor (TNF) receptor-associated factor)-associated NF-κB activator (TANK). Here we show that TANK is expressed in DRG neurons, that TANK expression is increased in response to peripheral nerve injury and that Sox11 overexpression in vitro increases TANK expression. Injury and in vitro overexpression were also found to preferentially increase TANK transcript variant 3 and a larger TANK protein isoform. To determine if Sox11 regulates TANK transcription bioinformatic analysis was used to identify potential Sox binding motifs within 5 kbp of the TANK 5’ untranslated region (UTR) across several mammalian genomes. Two sites in the mouse TANK gene were examined. Luciferase expression assays coupled with site-directed mutagenesis showed each site contributes to enhanced TANK promoter activity. In addition, chromatin immunoprecipitation assays showed direct Sox11 binding in regions containing the two identified Sox motifs in the mouse TANK 5’-UTR. These studies are the first to show that TANK is expressed in DRG neurons, that TANK is increased by peripheral nerve injury and that the regulation of TANK expression is, at least in part, controlled by the injury-associated transcription factor Sox11.
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影响因子：
5.3
作者：
Jing, Xiaotang;Wang, Ting;Huang, Shaohua;Glorioso, Joseph C.;Albers, Kathryn M.
通讯作者：
Albers, Kathryn M.
影响因子：
2.5
作者：
Kormish, Jay D.;Sinner, Debora;Zorn, Aaron M.
通讯作者：
Zorn, Aaron M.
影响因子：
3.4
作者：
Haslinger, Anja;Schwarz, Tobias J.;Lie, D. Chichung
通讯作者：
Lie, D. Chichung
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
14.9
作者：
UniProt Consortium
通讯作者：
UniProt Consortium