Comparison of NF-κB from the protists Capsaspora owczarzaki and Acanthoeca spectabilis reveals extensive evolutionary diversification of this transcription factor.

Comparison of NF-κB from the protists Capsaspora owczarzaki and Acanthoeca spectabilis reveals extensive evolutionary diversification of this transcription factor.
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比较原生物Capsaspora owczarzaki和Acanthoeca spectabilis的NF-κB,发现该转录因子具有广泛的进化多样性。

DOI:
10.1038/s42003-021-02924-2
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发表时间:
2021-12-16
影响因子:
5.9
通讯作者:
Gilmore TD
Gilmore TD
中科院分区:
生物学2区
文献类型:
--
作者:
Williams LM;Sridhar S;Samaroo J;Peart J;Adindu EK;Addanki A;DiRusso CJ;BB522 Molecular Biology Laboratory;Aguirre Carrión PJ;Rodriguez-Sastre N;Siggers T;Gilmore TD

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我们提供了原生生物中转录因子NF-κB的功能特征,并提供了关于这种生物学上重要的蛋白质的进化和多样化的信息。我们使用系统发育、细胞和生物化学技术对两种原生生物的NF-κB进行了表征。完整动物Capsaspora owczarzaki(Co)的NF-κB具有N端DNA结合结构域和C端Ankyrin repeat(ANK)结构域,其DNA结合特异性与后生动物NF-κB蛋白比与Rel蛋白更相似。ANK结构域的去除允许Co-NF-κB进入细胞核,结合DNA,并激活转录。然而,在人细胞中,IκB激酶不诱导Co-NF-κB的C-末端加工。Co-NF-κB在Co细胞中的过表达定位于胞浆。Co-NF-κB mRNA和DNA结合水平在三个Capsaspora生命阶段中不同。RNA测序和GO分析鉴定了Co-NF-κB的可能基因靶点。Acanthoeca acanthoabilis(As)的三种NF-κ B样蛋白含有保守的Rel同源结构域序列,但缺少C-末端ANK重复序列。所有三种As-NF-κB蛋白组成性地进入细胞核,但它们的DNA结合能力、转录激活活性和二聚化性质不同。这些结果提供了一个基础,了解这个关键的转录因子的进化起源,并可能有影响的起源调节免疫高等类群。转录因子NF-κ B是哺乳动物免疫的关键调节因子,但其在Capsaspora和领鞭毛虫等原生生物中的功能尚不清楚。在这里,Leah威廉姆斯等人表征和比较了来自Capsaspora和一种领鞭毛虫的NF-κ B的结构、活性和调节,为NF-κ B的起源提供了进一步的见解。
We provide a functional characterization of transcription factor NF-κB in protists and provide information about the evolution and diversification of this biologically important protein. We characterized NF-κB in two protists using phylogenetic, cellular, and biochemical techniques. NF-κB of the holozoan Capsaspora owczarzaki (Co) has an N-terminal DNA-binding domain and a C-terminal Ankyrin repeat (ANK) domain, and its DNA-binding specificity is more similar to metazoan NF-κB proteins than to Rel proteins. Removal of the ANK domain allows Co-NF-κB to enter the nucleus, bind DNA, and activate transcription. However, C-terminal processing of Co-NF-κB is not induced by IκB kinases in human cells. Overexpressed Co-NF-κB localizes to the cytoplasm in Co cells. Co-NF-κB mRNA and DNA-binding levels differ across three Capsaspora life stages. RNA-sequencing and GO analyses identify possible gene targets of Co-NF-κB. Three NF-κB-like proteins from the choanoflagellate Acanthoeca spectabilis (As) contain conserved Rel Homology domain sequences, but lack C-terminal ANK repeats. All three As-NF-κB proteins constitutively enter the nucleus of cells, but differ in their DNA-binding abilities, transcriptional activation activities, and dimerization properties. These results provide a basis for understanding the evolutionary origins of this key transcription factor and could have implications for the origins of regulated immunity in higher taxa. Transcription factor NF-ĸB is a key regulator of immunity in mammals, but its function in protists like Capsaspora and choanoflagellates is not known. Here, Leah Williams et al. characterize and compare the structure, activity, and regulation of NF-ĸB from Capsaspora and one choanoflagellate, providing further insight into the origins of NF-ĸB.
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