Abstract
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.
Highlights
1988; Ellisen et al 1991)
Structural Analysis of tan-1 in Cells with and without the t(7;9) To investigate the structure of the tan-1 proteins produced in cells containing or lacking the t(7;9)(q34;q34.3), antibodies raised against portions of the cytoplasmic domain of tan-1 were used in Western blot analysis of whole-cell extracts prepared from SUPT1 and Jurkat cells (Fig. 2)
Transfection of 293T cells with a cDNA beginning at bp 4015 and continuing through the 3' stop codon results in synthesis of several polypeptides of lower abundance, which are larger than those seen in SUP-T1 cells
Summary
ICT functions as a receptor in a signaling pathway (Fortini j'., ICTAT3 and Artavanis-Tsakonis 1993; Ghysen et al 1993). We believed that insights into the function of any of the several structural motifs within tan-1 might provide clues to the role of similar regions in the relatively large number of proteins that share these motifs. With these considerations in mind, we have proceeded in analysis of the TAN-1 gene along five different lines of investigation: (1) structural characterization of tan-1 in cells with and without the t(7;9)(q34;q34.3); (2) analysis of the subcellular location of tan-l; (3) in vivo transformation of murine bone marrow stem cells by TAN-1 cDNA; (4) identification of an intracellular ligand of tan-l; and (5) detection of a possible role for tan-1 in transcriptional activation
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