Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Interactions between HTLV-1 Tax and NF-kappa B/rel oncoproteins in T cells (Meeting abstract).
International Association for Comparative Research on Leukemia and Related Diseases, 16th Symposium. July 11-16, 1993, Montreal, Quebec, Canada, A18, 1993.. Unique Identifier : AIDSLINE ICDB/94698625 Lanoix J; Lacoste J; Pepin N; Le L; Roulston A; Rice N; Hiscott J; Lady Davis Inst., Jewish General Hospital and Dept. of; Microbiology and Immunology, McGill Univ., Montreal H3T 1E2,; Canada
Abstract:
Molecular, biochemical and epidemiological evidence strongly implicate HTLV-1 as an etiologic agent of adult T cell leukemia (ATL). The Tax protein of HTLV-1, a positive transcriptional activator of HTLV-1 gene expression is a viral oncogene that also increases transcription of cellular genes. One of the cellular targets of the trans-activating effects of Tax is the NF-kappaB/rel family of transcription factors, pleiotropic regulators of immunoregulatory, cytokine and viral gene expression. The trans-activation of NF-kappaB regulated (GGGACTTTCC) reporter gene activity was measured in co-expression studies using expression vectors for individual NF-kappaB subunits and the Tax protein. Tax behaved as a trans-dominant activator of NF-kappaB regulated reporter plasmid and could overcome the inhibitory effect of I kappaB alpha (MAD3), delta Rel-A(p65delta), a splicing variant of the Rel-A(p65) subunit, and the weakly trans-activating c-Rel protein. Analysis of NF-kappaB proteins in Jurkat T cells, Tax-expressing Jurkat cells (19D), and in HTLV-1 infected MT-2 cells by mobility shift and Western blot analyses with subunit specific antibodies revealed dynamic alterations in NF-kappa B binding activity and in the synthesis of NF-kappa B proteins. As characterized previously by Greene and colleagues, PMA induction of NF-kappa B binding activity in Jurkat cells was biphasic; at 2 hours after treatment, protein-DNA complexes were composed mainly of NFKB1 (p50) and Rel-A(p65) while at 24 hr, c-Rel and NFKB1 (p50) were the main subunits in protein-DNA complexes. In Tax expressing 19D cells, c-Rel and NFKB2(p52 or lyt-10) represented the main DNA binding activities. The correlation between Tax expression and specific NF-kappaB binding proteins was further strengthened with the observation that c-Rel and NFKB2 subunits were the major DNA binding forms in HTLV-1 producing MT-2 cells. Western blot analysis revealed 5- to 10-fold increases in the amounts of Rel-A (p65), c-Rel and NFKB2 (p52) proteins in both Tax-expressing 19D cells and HTLV-1 infected MT-2 cells. These results suggest that interaction of Tax with specific NF-kappa B/rel oncoproteins may be an important event leading to transformation of T cells by HTLV-1.
Keywords: Cell Transformation, Neoplastic DNA, Neoplasm/METABOLISM Gene Products, tax/*METABOLISM Human HTLV-I Infections/METABOLISM NF-kappa B/*METABOLISM Proto-Oncogene Proteins/*METABOLISM RNA Splicing T-Lymphocytes/*METABOLISM/PATHOLOGY ABSTRACT 940730
M9470927
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Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
