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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.

Pubmed ID: 8642313


  • Guan E
  • Wang J
  • Laborda J
  • Norcross M
  • Baeuerle PA
  • Hoffman T


The Journal of experimental medicine

Publication Data

May 1, 1996

Associated Grants


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