THE ANKYRIN REPEAT DOMAINS OF THE NF-KAPPA-B PRECURSOR P105 AND THE PROTOONCOGENE BCL-3 ACT AS SPECIFIC INHIBITORS OF NF-KAPPA-B DNA-BINDING
THE ANKYRIN REPEAT DOMAINS OF THE NF-KAPPA-B PRECURSOR P105 AND THE PROTOONCOGENE BCL-3 ACT AS SPECIFIC INHIBITORS OF NF-KAPPA-B DNA-BINDING
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DOI：
10.1073/pnas.89.6.2489
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发表时间：
1992-03-15
影响因子：
11.1
通讯作者：
SCHEIDEREIT, C
中科院分区：
文献类型：
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作者：
HATADA, EN;NIETERS, A;SCHEIDEREIT, C
诱导型多效性转录因子NF-κ-B由两个亚基p50和p65组成。p50亚基在105-kDa开放阅读框架的N-末端一半上编码，并且含有rel样结构域。到目前为止，还没有描述C-末端部分的功能。我们发现，当p105的C-末端的一半作为一个单独的分子表达时，与p50结合，并能迅速破坏p50或天然NF-κ-B的蛋白质-DNA复合物。缺失分析的这种抑制剂衍生的抑制剂活性表明域含有锚样重复作为抑制所必需的。含有7个锚蛋白重复序列的原癌基因bcl-3同样可以抑制p50 DNA结合。这些观察结果确定bcl-3作为NF-κ-B的抑制剂，并强烈表明这些因子中的锚蛋白重复序列参与与p50的rel样结构域的蛋白质-蛋白质相互作用。与其他含锚蛋白重复序列的蛋白质的比较表明，这些蛋白质的一个亚类作为调控因子的rel样转录因子。
The inducible pleiotropic transcription factor NF-kappa-B is composed of two subunits, p50 and p65. The p50 subunit is encoded on the N-terminal half of a 105-kDa open reading frame and contains a rel-like domain. To date, no function has been described for the C-terminal portion. We show here that the C-terminal half of p105, when expressed as a separate molecule, binds to p50 and can rapidly disrupt protein-DNA complexes of p50 or native NF-kappa-B. Deletion analysis of this precursor-derived inhibitor activity indicated a domain containing ankyrin-like repeats as necessary for inhibition. The protooncogene bcl-3, which contains seven ankyrin repeats, can equally inhibit p50 DNA binding. These observations identify bcl-3 as an inhibitor of NF-kappa-B and strongly suggest that the ankyrin repeats in these factors are involved in protein-protein interactions with the rel-like domain of p50. Comparison with other ankyrin repeat-containing proteins suggests that a subclass of these proteins acts as regulators of rel-like transcription factors.