Comparative distribution of protein components of the A20 ubiquitin-editing complex in normal human brain.
Comparative distribution of protein components of the A20 ubiquitin-editing complex in normal human brain.
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DOI：
10.1016/j.neulet.2012.05.043
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发表时间：
2012-06-27
影响因子：
2.5
通讯作者：
Betarbet RS
中科院分区：
文献类型：
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作者：
Pranski EL;Van Sanford CD;Dalal NV;Orr AL;Karmali D;Cooper DS;Costa N;Heilman CJ;Gearing M;Lah JJ;Levey AI;Betarbet RS
先天和获得性免疫反应的激活受到严格的调控，因为激活不足可能导致病原体的缺陷清除，而过度激活可能导致致命性全身炎症或自身免疫。A20通过抑制NF-κB的激活，发挥天然免疫和获得性免疫的负调节作用。A20通过与RNF11和Itch、E3泛素连接酶和接头蛋白TAX1BP1等其他蛋白的复合体介导其抑制功能。由于NF-κB与多种神经功能密切相关，我们预测其抑制物A20复合体也存在于神经系统中。为了更好地了解A20复合体和NF-κB信号通路的作用，我们测定了A20mRNA的区域分布以及RNF11、TAX1BP1和ITCH的蛋白表达水平和在不同脑区的分布。TRAF6也是一种E3连接酶，在NF-κB信号通路中起重要作用，因此对TRAF6的分布也进行了研究。我们的研究首次描述并证明了A20泛素编辑复合体的基本成分存在，并主要在神经元中表达。A20复杂成分在整个人脑中也有不同的表达。这项研究提供了关于A20复杂成分的区域特异性表达的有用信息，这对于确定NF-κB信号通路在神经元发育和退化中的作用将是非常有价值的。
Activation of innate and adaptive immune responses is tightly regulated, as insufficient activation could result in defective clearance of pathogens, while excessive activation might lead to lethal systemic inflammation or autoimmunity. A20 functions as a negative regulator of innate and adaptive immunity by inhibiting NF-κB activation. A20 mediates its inhibitory function in a complex with other proteins including RNF11 and Itch, both E3 ubiquitin ligases and TAX1BP1, an adaptor protein. Since NF-κB has been strongly implicated in various neuronal functions, we predict that its inhibitor, the A20 complex, is also present in the nervous system. In efforts to better understand the role of A20 complex and NF-κB signaling pathway, we determined regional distribution of A20 mRNA as well as protein expression levels and distribution of RNF11, TAX1BP1 and Itch, in different brain regions. The distribution of TRAF6 was also investigated since TRAF6, also an E3 ligase, has an important role in NF-κB signaling pathway. Our investigations, for the first time, describe and demonstrate that the essential components of the A20 ubiquitin-editing complex are present and mainly expressed in neurons. The A20 complex components are also differentially expressed throughout the human brain. This study provides useful information about region specific expression of the A20 complex components that will be invaluable while determining the role of NF-κB signaling pathway in neuronal development and degeneration.
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影响因子：
3.7
作者：
Imielski Y;Schwamborn JC;Lüningschrör P;Heimann P;Holzberg M;Werner H;Leske O;Püschel AW;Memet S;Heumann R;Israel A;Kaltschmidt C;Kaltschmidt B
通讯作者：
Kaltschmidt B
DOI：
10.1073/pnas.0404132101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Ea, CK;Sun, L;Chen, ZJJ
通讯作者：
Chen, ZJJ
影响因子：
11.2
作者：
Hicks, AA;Pétursson, H;Sveinbjörnsdóttir, S
通讯作者：
Sveinbjörnsdóttir, S
影响因子：
56.9
作者：
Lee, EG;Boone, DL;Ma, A
通讯作者：
Ma, A
DOI：
10.1038/mt.2008.146
发表时间：
2008-09
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
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