PMID- 8417807 OWN - NLM STAT- MEDLINE DCOM- 19930203 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 81 IP - 1 DP - 1993 Jan 1 TI - Human T-lymphotropic virus type I tax regulates the expression of the human lymphotoxin gene. PG - 95-100 AB - Human T-lymphotropic virus type-I (HTLV-I)-infected T-cell lines constitutively produce high levels of lymphotoxin (LT). To analyze the mechanisms that lead to the expression of LT in HTLV-I-infected cell lines, we studied regulatory regions of the human LT promoter involved in the activation of the human LT gene. As determined by deletional analysis, sequences between +137 and -116 (relative to the transcription initiation site) are sufficient to direct expression of a reporter gene in the HTLV-I-infected cell line MT-2. Site-directed mutation of a of the single kappa B-like motif present in the LT promoter region (positions -99 to -89) completely abrogated LT promoter activity in MT-2 cells, suggesting that this site plays a critical role in the activation of the human LT gene. Transfection of LT constructs into HTLV-I-uninfected and -unstimulated Jurkat and U937 cell lines showed little to no activity of the LT promoter. Cotransfection of the same constructs with a tax expression plasmid into Jurkat cells led to detectable promoter activity, which could be significantly increased by stimulation of the cells with phorbol myristate acetate (PMA). Similarly, cotransfection of the LT promoter constructs and the tax expression plasmid into U937 cells led to significant promoter activity upon stimulation with PMA. These data suggest that HTLV-I tax is involved in the upregulation of LT gene expression in HTLV-I-infected cells. FAU - Tschachler, E AU - Tschachler E AD - Department of Dermatology, University of Vienna Medical School, Austria. FAU - Bohnlein, E AU - Bohnlein E FAU - Felzmann, S AU - Felzmann S FAU - Reitz, M S Jr AU - Reitz MS Jr LA - eng PT - Journal Article PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Lymphotoxin-alpha) RN - 0 (NF-kappa B) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM GS - tax MH - Animals MH - Base Sequence MH - Binding Sites MH - Cell Line MH - *Gene Expression Regulation MH - *Genes, pX MH - Human T-lymphotropic virus 1/*genetics MH - Humans MH - Lymphotoxin-alpha/*genetics MH - Mice MH - Molecular Sequence Data MH - Mutagenesis, Site-Directed MH - NF-kappa B/metabolism MH - Plasmids MH - Polymerase Chain Reaction MH - Promoter Regions, Genetic MH - Regulatory Sequences, Nucleic Acid MH - Tetradecanoylphorbol Acetate/pharmacology MH - Transfection EDAT- 1993/01/01 00:00 MHDA- 2001/03/28 10:01 CRDT- 1993/01/01 00:00 PHST- 1993/01/01 00:00 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1993/01/01 00:00 [entrez] AID - S0006-4971(20)73300-8 [pii] PST - ppublish SO - Blood. 1993 Jan 1;81(1):95-100.