Functional Analysis of the TAN-1 Gene, a Human Homolog of Drosophila Notch

  1. J. Aster*,
  2. W. Pear,
  3. R. Hasserjian*,
  4. H. Erba*,,
  5. F. Davi*,
  6. B. Luo*,
  7. M. Scott,
  8. D. Baltimore, and
  9. J. Sklar*
  1. *Division of Molecular Oncology, Department of Pathology, and Division of Hematology-Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142

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Excerpt

The TAN-1 gene was originally discovered at the breakpoint of a recurrent (7;9)(q34;q34.3) chromosomal translocation found in a subset of human T-lymphoblastic leukemias (Reynolds et al. 1987; Smith et al. 1988; Ellisen et al. 1991). This translocation joins roughly the 3′ half of TAN-1 head-to-head with the 3′ portion of the β T-cell-receptor gene (TCRB) beginning at the 5′ boundary of one or the other J segment. Intact TAN-1 is normally transcribed into an 8.2-kb transcript that is present in many tissues, most abundantly in developing thymus and spleen (Ellisen et al. 1991). This tissue distribution and the apparent involvement of an altered version of the gene in T-cell cancers have suggested that TAN-1 normally has some special function in lymphocytes or their precursors.

Nucleotide sequence analysis of the TAN-1 transcript has revealed a single open reading frame of 2555 codons. The predicted amino acid sequence is highly homologous to...

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