       Document 0069
 DOCN  M9550069
 TI    Immediate effects of reversible HTLV-1 tax function: T-cell activation
       and apoptosis.
 DT    9505
 AU    Chlichlia K; Moldenhauer G; Daniel PT; Busslinger M; Gazzolo L;
       Schirrmacher V; Khazaie K; Department of Tumor Immunology, German Cancer
       Research Center,; Heidelberg.
 SO    Oncogene. 1995 Jan 19;10(2):269-77. Unique Identifier : AIDSLINE
       MED/95140416
 AB    The tax protein of Human T-cell leukemia virus type 1 (HTLV-1) is
       important for the transforming properties of this virus in vitro and is
       considered to be responsible for the early stages of leukemogenesis in
       infected hosts. To address the early consequences of HTLV-1 tax
       function, we have constructed fusion proteins containing tax sequence
       either aminoterminal (taxER) or carboxy-terminal (ERtax) of the hormone
       binding domain of the human estrogen receptor (ER). Addition of estrogen
       or the antagonist hydroxytamoxifen to Jurkat T-cells expressing these
       constructs led to the trans-activation or responsive promoters and
       upregulation of cell surface markers CD28, CD69 and CD5 but not CD25
       (IL2R-alpha subunit) or B7 (ligand for CD28). Additional stimulation of
       the T-cell receptor CD3 complex, led to the upregulation of CD25. B7 was
       upregulated by concomittent activation of ERtax and CD3 or CD28
       pathways. These events were in part reversible upon withdrawal of
       hormone and inactivation of ERtax. Severe inhibition of proliferation,
       and apoptosis was observed with cells which had been subjected to short
       term (3 days) activation of the tax fusion proteins and the CD3 complex.
       Induction of ERtax activity for longer than 3 days promoted cell death
       independently of CD3 stimulation. Co-stimulation through the CD28 cell
       surface molecule did not suppress induction of apoptosis.
 DE    Antigens, CD28/BIOSYNTHESIS  Antigens, CD3/BIOSYNTHESIS  *Apoptosis
       Cell Division  Estrogens/PHARMACOLOGY  Flow Cytometry  Gene Products,
       tax/GENETICS/*METABOLISM  Human  HTLV-I/*METABOLISM  Lymphocyte
       Transformation  Receptors, Estrogen/GENETICS  Recombinant Proteins
       Support, Non-U.S. Gov't  T-Lymphocytes/*IMMUNOLOGY  Time Factors
       Trans-Activation (Genetics)  Tumor Cells, Cultured  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

