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PMID: 3037548 Published · ppublish English Journal Article

Activation of interleukin 2 and interleukin 2 receptor (Tac) promoter expression by the trans-activator (tat) gene product of human T-cell leukemia virus, type I.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 84 ·No. 15 ·1987-08-00 ·Pages 5389-93

Siekevitz M, Feinberg MB, Holbrook N, Wong-Staal F, Greene WC

Abstract

Cotransfection of cDNA encoding the trans-activator gene product of human T-cell leukemia virus, type I (HTLV-I) (tat-I), which acts in trans to augment viral gene expression, has revealed strong regulatory effects of this viral protein on the inducible cellular promoters governing human interleukin 2 (IL-2) and IL-2 receptor (Tac) gene expression. The tat-I protein stimulates a 3- to 6-fold increase in IL-2 receptor (Tac) promoter activity in transfected Jurkat T cells, but not in the natural killer-like YT cell line, as measured by changes in the expression of the chloramphenicol acetyltransferase (CAT; EC 2.3.1.28) reporter gene linked to this promoter. In contrast, tat-I alone has little or no effect on IL-2 promoter activity in Jurkat T cells but markedly synergizes with other mitogenic stimuli (phytohemagglutinin, phorbol 12-myristate 13-acetate, or the OKT3 monoclonal antibody), which alone are ineffective. The tat-I protein also partially circumvents the pronounced inhibitory effects of cyclosporin A on the IL-2 promoter. Other cellular and viral promoters are unaffected by the tat-I gene product, either alone or in combination with other mitogens. The specific effects of the tat-I gene product on the IL-2 and IL-2 receptor (Tac) promoters suggest the possibility of an autocrine or paracrine mechanism of T-cell growth as an early event in HTLV-I-mediated leukemogenesis.

MeSH Terms
Acetyltransferases/genetics Animals Chloramphenicol O-Acetyltransferase Cyclosporins/pharmacology Deltaretrovirus/genetics Gene Expression Regulation/drug effects Gene Products, tat Interleukin-2/genetics Phytohemagglutinins/pharmacology Plasmids Promoter Regions, Genetic Receptors, Immunologic/genetics Receptors, Interleukin-2 Tetradecanoylphorbol Acetate/pharmacology Transcription Factors/pharmacology Transfection
Chemicals
Cyclosporins Gene Products, tat Interleukin-2 Phytohemagglutinins Receptors, Immunologic Receptors, Interleukin-2 Transcription Factors Acetyltransferases Chloramphenicol O-Acetyltransferase Tetradecanoylphorbol Acetate
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Siekevitz M
Feinberg M B
Holbrook N
Wong-Staal F
Greene W C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.84.15.5389
Published
1987-08-00
Pages
5389-93
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC298861
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.84.15.5389 PMC Full Text View journal details
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