Transactivation of the c-myc promoter by human T cell leukemia virus type 1 tax is mediated by NF kappa B.
Human T cell leukemia virus type 1 is the causative agent of adult T cell leukemia. The virus encodes a 40-kDa protein, tax, that is important for the immortalization of T cells. Expression of tax activates several cellular transcription factors, including NF kappa B. We have previously identified two functional NF kappa B binding sites within the murine c-myc gene: upstream regulatory element (URE) and internal regulatory element (IRE). Using transient cotransfection analysis of Jurkat or HeLa cells, we report that tax can transactivate chimeric TK-CAT constructs containing multiple copies of wild-type URE or IRE, but not constructs with mutated versions of these elements. Furthermore, tax induced transcriptional activity of murine and human c-myc promoter-CAT hybrid genes in Jurkat and HeLa cells. A mutated tax expression vector, which fails to activate NF kappa B, was unable to induce either murine or human c-myc-CAT or URE/IRE-TK-CAT constructs. Mutant c-myc gene-CAT constructs, in which the URE and IRE were mutated either singly or in combination by site directed mutagenesis, displayed significantly reduced CAT activation upon cotransfection with a tax expression vector. These results suggest that tax can transactivate the c-myc gene through NF kappa B. The tax-induced stimulation of this oncogene may play a role in T cell immortalization.
Duyao
M P
MP
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
Kessler
D J
DJ
Spicer
D B
DB
Bartholomew
C
C
Cleveland
J L
JL
Siekevitz
M
M
Sonenshein
G E
GE
D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D016259:Genes, myc; D016355:Genes, pX; D005822:Genetic Vectors; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D015533:Transcriptional Activation; D014162:Transfection
D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D015500:Chloramphenicol O-Acetyltransferase