T cell leukemia-associated human Notch/translocation-associated Notch homologue has I kappa B-like activity and physically interacts with nuclear factor-kappa B proteins in T cells.
T cell leukemia-associated human Notch/translocation-associated Notch homologue has I kappa B-like activity and physically interacts with nuclear factor-kappa B proteins in T cells.
复制标题
T细胞白血病相关的人缺口/易位相关的Notch同源物具有kappa b样活性，并与T细胞中的核因子-kappa B蛋白物理相互作用。
DOI：
10.1084/jem.183.5.2025
复制
发表时间：
1996-05-01
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
易位相关Notch同源物（TAN-1）是最初从携带9：7（q34.3）易位的人T细胞白血病的易位断点克隆的基因，其编码属于Notch/Lin-12/Glp-1受体家族的蛋白质。这些受体在无脊椎动物和脊椎动物的发育过程中介导许多细胞命运的特化。Notch/TAN-1的细胞内部分含有六个锚蛋白重复序列，其与在细胞质I κ B蛋白中发现的那些相似。I κ B蛋白是核因子（NF）-κ B/Rel转录因子的特异性抑制剂。在这里，我们表明，TAN-1具有I κ B样调节因子的功能特性，对NF-κ B p50亚基具有特异性。与TAN- 1的胞质部分对应的重组多肽（TAN-1C）特异性地抑制含p50的NF-κ B复合物的DNA结合。当在适当的细胞系中过表达时，TAN- 1C以类似于结构相关蛋白Bcl-3的方式在瞬时报告基因测定中阻止κ B依赖性反式激活。TAN-1C可通过减弱过量p50同源二聚体的抑制作用来激活κ B依赖性基因表达。免疫沉淀实验表明，来自T细胞系的TAN-1与含有p50和p65亚基的NF-κ B相关。这些观察结果表明，TAN-1C可能直接参与NF-κ B B转录因子和调节核基因表达。
Translocation-associated Notch homologue (TAN-1), a gene originally cloned from the translocation breakpoint of a human T cell leukemia carrying a 9:7(q34.3) translocation, encodes a protein belonging to the Notch/Lin-12/Glp-1 receptor family. These receptors mediate the specification of numerous cell fates during development in invertebrates and vertebrates. The intracellular portion of Notch/TAN-1 contains six ankyrin repeats that are similar to those found in cytoplasmic I kappa B proteins. I kappa B proteins are specific inhibitors of nuclear factor (NF)-kappa B/Rel transcription factors. Here we show that TAN-1 has functional properties of an I kappa B-like regulator with specificity for the NF-kappa B p50 subunit. A recombinant polypeptide corresponding to the cytoplasmic portion of TAN- 1 (TAN-1C) specifically inhibited the DNA binding of p50-containing NF- kappa B complexes. When overexpressed in an appropriate cell line, TAN- 1C prevented kappa B-dependent transactivation in transient reporter gene assays in a fashion similar to the structurally related protein, Bcl-3. TAN-1C could activate kappa B-dependent gene expression by attenuating the inhibitory effect of an excess of p50 homodimers. Immunoprecipitation experiments showed that the TAN-1 from a T cell line is associated with NF-kappa B containing p50 and p65 subunits. These observations indicate that TAN-1C may directly engage NF-kappa B transcription factors and modulate nuclear gene expression.