NAC1, a POZ/BTB protein that functions as a corepressor
NAC1, a POZ/BTB protein that functions as a corepressor
复制标题
DOI：
10.1016/j.neuint.2008.12.008
复制
发表时间：
2009-03-01
影响因子：
4.2
通讯作者：
Mackler, Scott A.
中科院分区：
文献类型：
--
作者：
Korutla, Laxminarayana;Wang, Peijie;Mackler, Scott A.
我们现在证明，NAC 1作为其他POZ/BTB蛋白的辅阻遏物。NAC 1是一种含有POZ/BTB基序的转录抑制蛋白。在神经元（N2 A）细胞和非神经元（HEK 293 T）细胞中的哺乳动物双杂交测定中，用Gal 4-ZID、Gal 4-BCL 6、Gal 4-ZF 5和kelch蛋白Gal 4-MAYVEN和Gal 4-NRP/B融合蛋白标记的VP 16活化结构域导致转录抑制的显著逆转。我们还观察到另一种辅阻遏物BCoR Gal 4融合蛋白的类似结果。在Gal 4-DBD融合瞬时测定中，NAC 1增强了ZF 5介导的阻遏。GST pulldown分析进一步证实了这些蛋白质与NAC 1之间的蛋白质-蛋白质相互作用。两种NAC 1亚型都表现出通过POZ/BTB结构域而不是与非POZ/BTB区域的选择性相互作用。内源性NAC 1和BCL 6在CNS区域中物理相关。引人注目的是，NAC 1没有与早幼粒细胞白血病锌指蛋白（PLZF）相互作用，PLZF是另一种在成人大脑中未发现的POZ/BTB蛋白。因此，我们得出结论，NAC 1作为一个辅阻遏物的POZ/BTB蛋白在成熟的中枢神经系统中表达的功能。(C)2008爱思唯尔有限公司保留所有权利。
We now demonstrate that NAC1 acts as a corepressor for other POZ/BTB proteins. NAC1 is a POZ/BTB motif containing transcriptional repressor protein. In a mammalian two hybrid assay in neuronal (N2A) cells and non-neuronal (HEK 293T) cells, VP16 activation domain tagged NAC1 resulted in significant reversal of transcriptional inhibition with the Gal4-ZID, Gal4-BCL6, Gal4-ZF5, and kelch proteins Gal4-MAYVEN and Gal4-NRP/B fusion proteins. We also observed similar results with another corepressor, BCoR Gal4 fusion protein. NAC1 potentiated ZF5 mediated repression in Gal4-DBD fusion transient assays. GST pulldown assays further confirmed protein-protein interactions between these proteins and NAC1. Both the NAC1 isoforms demonstrated selective interaction through the POZ/BTB domain but not with the non-POZ/BTB region. Endogenous NAC1 and BCL6 physically associated in CNS regions. Strikingly, NAC1 did not interact with the pro-myelocytic leukemia zinc finger protein (PLZF), another POZ/BTB protein that is not found in the adult brain. Therefore, we conclude that NAC1 functions as a corepressor for POZ/BTB proteins expressed in the mature CNS. (C) 2008 Elsevier Ltd. All rights reserved.