Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
Role of nuclear factor-kB in the regulation of c-myc gene transcription.
Diss Abstr Int [B]; 53(3):1192 1992. Unique Identifier : AIDSLINE ICDB/93687843 Duyao MP; Boston Univ.
Abstract:
The c-myc proto-oncogene has been implicated in cell proliferation, differentiation, and neoplasia. Its expression is largely regulated at the level of transcription. I have mapped several regions upstream of the murine c-myc promoter which interact with nuclear proteins from the murine B-cell lymphoma cell line WEHI 231. These interactions were decreased upon antiserum-induced growth arrest of these cells and during the down-modulation of c-myc gene transcription. One of these regions, termed URE, is located -1101 to -1081 bp relative to the first transcription start site. Interaction of nuclear factor kappa B (NFkB) with the URE was demonstrated based on (1) binding competition with oligonucleotides containing known NFkB sites from various genes, (2) induction of binding during differentiation of 70Z/3 pre-B cells to B cells, (3) induction of binding following treatment of cytoplasmic pre-B-cell extracts with detergents, and (4) the enhancement of binding by GTP. Upon induction of NFkB, stimulation of transiently transfected thymidine kinase promoter-driven chloramphenicol acetyl transferase (CAT) gene constructs containing multiple copies of the URE indicated that the URE is a functional NFkB element, mediating positive activation of transcription. The URE is one of two NFkB sites present in the gene; the other is termed IRE and is located within exon 1 at +440 to +459 bp. To assess the role of NFkB in regulation of c-myc transcription, the effect of the human T-cell leukemia virus type I tax protein, which induces NFkB expression, was examined. In transient cotransfection analyses of Jurkat or HeLa cells, tax transactivated murine c-myc promoter/exon 1 CAT constructs containing wild-type URE and IRE elements. In contrast, tax activation of mutated myc CAT constructs, in which the URE and IRE were altered to prevent binding of NFkB, was significantly reduced. Furthermore, a mutant tax protein, unable to induce NFkB, failed to activate these constructs. Thus, tax transactivation of c-myc is mediated through the interaction of NFkB. These findings suggest that activation of c-myc expression via activation of NFkB may play an important role in c-myc transcription. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD92-20756.)
Keywords: *Cell Division Chloramphenicol Acetyltransferase/GENETICS Exons Gene Expression Regulation Gene Products, tax/GENETICS Lymphoma, B-Cell/GENETICS NF-kappa B/GENETICS Promoter Regions (Genetics) Proto-Oncogene Proteins c-myc/*GENETICS *Transcription, Genetic Tumor Cells, Cultured THESIS 930228
M9320862
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Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
