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.
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.
Mesh Terms:
Animals, Cell Line, Chromosome Mapping, Chromosomes, Human, Pair 7, Chromosomes, Human, Pair 9, Humans, Invertebrates, Leukemia, T-Cell, Membrane Proteins, NF-kappa B, Proto-Oncogene Proteins, Receptor, Notch1, Receptors, Cell Surface, Receptors, Notch, Recombinant Fusion Proteins, T-Lymphocytes, Transcription Factor RelB, Transcription Factors, Transcriptional Activation, Translocation, Genetic, Tumor Cells, Cultured, Vertebrates
Animals, Cell Line, Chromosome Mapping, Chromosomes, Human, Pair 7, Chromosomes, Human, Pair 9, Humans, Invertebrates, Leukemia, T-Cell, Membrane Proteins, NF-kappa B, Proto-Oncogene Proteins, Receptor, Notch1, Receptors, Cell Surface, Receptors, Notch, Recombinant Fusion Proteins, T-Lymphocytes, Transcription Factor RelB, Transcription Factors, Transcriptional Activation, Translocation, Genetic, Tumor Cells, Cultured, Vertebrates
J. Exp. Med.
Date: May. 01, 1996
PubMed ID: 8642313
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