High levels of the DNA-binding activity of E2F in adult T-cell leukemia and human T-cell leukemia virus type I-infected cells: possible enhancement of DNA-binding of E2F by the human T-cell leukemia virus I transactivating protein, Tax.
Transcription factor E2F binds to cellular promoters of certain growth- and cell cycle-controlling genes and forms distinct heteromeric complexes with other nuclear proteins. It has therefore been proposed that E2F is involved in cellular proliferation control. Human T-cell leukemia virus type I (HTLV-I) is an etiological agent of adult T-cell leukemia (ATL). We show here by mobility-shift assay that E2F-containing DNA-binding complexes were detected in HTLV-I-infected T-cell lines and leukemic cells obtained from ATL patients but not in an uninfected T-cell line, Jurkat, and normal peripheral blood mononuclear cells. The Tax protein, encoded by HTLV-I, is a potent transcription activator of viral and several cellular genes. We demonstrate that expression of Tax can induce the E2F-containing DNA-binding complexes in Jurkat T cells. Thus, Tax, through enhancement of the DNA-binding activity of E2F, may be capable of regulating cellular gene expression implicated in the proliferation and transformation of T cells in ATL. This activity may be relevant to the mechanisms whereby HTLV-I which does not contain oncogenes induces neoplasia.
Mori
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First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
D000328:Adult; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000302:isolation & purification / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050684:E2F Transcription Factors; D016259:Genes, myc; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D015458:Leukemia, T-Cell / Q000378:metabolism*; D051379:Mice; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D056465:Retinoblastoma-Binding Protein 1; D013601:T-Lymphocytes / Q000378:metabolism*; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism*
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D009838:Oligodeoxyribonucleotides; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D004247:DNA