       Document 0152
 DOCN  M9440152
 TI    Overproduction of NFKB2 (lyt-10) and c-Rel: a mechanism for HTLV-I
       Tax-mediated trans-activation via the NF-kappa B signalling pathway.
 DT    9404
 AU    Lanoix J; Lacoste J; Pepin N; Rice N; Hiscott J; Terry Fox Molecular
       Oncology Group, Abe Stern Cancer Research; Laboratory, Lady Davis
       Institute for Medical Research, Sir; Mortimer B. Davis-Jewish General
       Hospital, Montreal, Quebec,; Canada.
 SO    Oncogene. 1994 Mar;9(3):841-52. Unique Identifier : AIDSLINE
       MED/94151007
 AB    Molecular, biochemical and epidemiological evidence implicate HTLV-I as
       an etiologic agent of adult T cell leukemia (ATL). The Tax protein of
       HTLV-I, a positive transcriptional activator of HTLV-I gene expression,
       is a viral oncogene that also increases transcription of cellular genes
       including GM-CSF, IL-2R alpha and IL-2. One of the cellular targets of
       the trans-activating effects of Tax is the NF-kappa B/Rel family of
       transcription factors, pleiotropic regulators of immunoregulatory,
       cytokine and viral gene expression. In this report, we demonstrate that
       NFKB2 (lyt-10) and c-Rel are overexpressed in HTLV-I infected and
       Tax-expressing cells and, together, account for the majority of the
       constitutive NF-kappa B binding activity in these cells before and after
       PMA stimulation. Most importantly, we show a Tax-dependent correlation
       between expression of NFKB2(p100) and processing to the DNA binding
       NFKB2(p52) form, induction of c-Rel, and trans-activation of NF-kappa
       B-mediated gene expression. Furthermore, the NFKB2 precursor is
       physically associated with c-Rel and with Tax in HTLV-I infected cells.
       We propose that NFKB2 synthesis and processing allows continuous nuclear
       expression of an otherwise cytoplasmic protein and, in conjunction with
       overexpression of c-Rel, NFKB2 alters the NF-kappa B signalling pathway
       and contributes to leukemic transformation of T cells by HTLV-I.
 DE    Base Sequence  Cell Line  Cell Transformation, Viral  Gene Expression
       Regulation  Gene Products, tax/*GENETICS  Human  HTLV-I/*GENETICS
       Molecular Sequence Data  NF-kappa B/*BIOSYNTHESIS/GENETICS/*METABOLISM
       Oligodeoxyribonucleotides  Protein Processing, Post-Translational
       Proto-Oncogene Proteins/*BIOSYNTHESIS/GENETICS/METABOLISM  *Signal
       Transduction  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       T-Lymphocytes/METABOLISM/MICROBIOLOGY  *Trans-Activation (Genetics)
       JOURNAL ARTICLE

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

