Endoproteolytic processing of C-terminally truncated NF-κB2 precursors at κB-containing promoters
Endoproteolytic processing of C-terminally truncated NF-κB2 precursors at κB-containing promoters
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DOI：
10.1073/pnas.0609914104
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发表时间：
2007-03-27
影响因子：
11.1
通讯作者：
Xiao, Gutian
中科院分区：
文献类型：
--
作者：
Qing, Guoliang;Qu, Zhaoxia;Xiao, Gutian
NF-κ B2/p52前体p100、p100 Delta Cs的C-末端部分截短形式表现出组成性加工和致癌能力，尽管负责的机制仍然未知。在这里，我们报告说，p100三角洲Cs的具体处理与结合到启动子DNA-含有KB网站。在细胞核中，p100 Delta C与κ B启动子DNA结合，随后募集蛋白酶体形成稳定的蛋白酶体/p100 Delta C/DNA复合物，其介导p100 Delta C的加工。值得注意的是，在KB启动子处的加工是由蛋白酶体介导的在p100 Delta Cs的氨基酸Dots处的内切蛋白水解切割启动的，并且加工的p52（而不是前体本身）通过上调靶基因的子集而致癌。我们的研究表明，p100加工的不同机制，并提出证据表明，蛋白酶体调节转录因子的作用，在启动子区域通过endoproteolysis。
The C-terminal, partially truncated forms of the NF-kappa B2/p52 precursor p100, p100 Delta Cs, manifest constitutive processing and oncogenic ability, although the responsible mechanisms remain unknown. Here, we report that p100 Delta Cs are specifically processed in association with binding to promoter DNA-containing KB sites. In the nucleus, p100 Delta Cs bind to the kappa B promoter DNA and subsequently recruit the proteasome to form a stable proteasome/p100 Delta C/DNA complex, which mediates the processing of p100 Delta Cs. Notably, the processing at the KB promoter is initiated by a proteasome-mediated endoproteolytic cleavage at amino acid Dots of p100 Delta Cs, and the processed p52, but not the precursors themselves, is oncogenic by up-regulating a subset of target genes. Our studies demonstrate a different mechanism of p100 processing and also present evidence showing that the proteasome modulates the action of transcription factors at promoter regions through endoproteolysis.