SGT1 is essential for Nod1 activation
SGT1 is essential for Nod1 activation
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DOI：
10.1073/pnas.0610926104
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发表时间：
2007-04-17
影响因子：
11.1
通讯作者：
Ulevitch, Richard
中科院分区：
文献类型：
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作者：
Correia, Jean da Silva;Miranda, Yvonne;Ulevitch, Richard
人类的点状受体家族含有识别入侵细菌的蛋白质。Nod1是这个家族的成员之一，它被含有中位二氨基戊二酸的特定肽聚糖衍生的神经肽激活。植物含有一个被称为抗性(R)蛋白的大家族，它们与NOD样受体具有共同的结构特征，对于抵御各种植物病原体是必不可少的。广泛的遗传学研究表明，R蛋白的功能由多种蛋白质决定，包括SGT1、RAR1和HSP90。在这里，我们证明了SGT1正向调节Nod的激活。用siRNA耗尽SGT1不会影响Nod1蛋白或下游信号分子的稳定性，但会阻止与Nod1激活相关的多种细胞反应。相反，哺乳动物中RAR1的同源基因Chp1的缺失对依赖Nod1的细胞激活没有影响。最后，HSP90的缺失或添加HSP90的药物抑制剂会导致Nod1蛋白的丢失。因此，我们展示了植物R蛋白和人类Nod1依赖途径中共同的调控途径，为理解Nod1途径提供了基础。
The Nod-like receptor family in man contains proteins that recognize invasive bacteria. Nod1, a member of this family, is activated by specific pepticloglycan-derived muropeptides that contain meso-diaminopimelic acid. Plants contain a large family of proteins known as resistance (R) proteins that have common structural features with the Nod-like receptors and are essential for protection against a variety of plant pathogens. Extensive genetic studies have shown that the R protein function is determined by multiple proteins including SGT1, Rar1, and HSP90. Here we show that SGT1 positively regulates Nod activation. Depletion of SGT1 with siRNA aid not affect stability of Nod1 protein or of downstream signaling molecules but did prevent multiple cellular responses associated with Nod1 activation. In contrast, depletion of the mammalian orthologue of Rar1, Chp1, had no effect on Nod1-dependent cellular activation. Finally, depletion of HSP90 or addition of a pharmacologic inhibitor of HSP90 resulted in loss of Nod1 protein. Thus, we show common regulatory pathways in plant R protein and human Nod1-dependent pathways and provide the basis for understanding the Nod1 pathway.