Human T cell lymphotropic virus type I Tax activates IL-15R alpha gene expression through an NF-kappa B site.
IL-15 mRNA levels are increased in diseases caused by human T cell lymphotropic virus type I (HTLV-I). In this study, we demonstrated that IL-15Ralpha, the IL-15-specific binding receptor, mRNA and protein levels were also elevated in HTLV-I-infected cells. We showed that transient HTLV-I Tax expression lead to increased IL-15Ralpha mRNA levels. In addition, by using a reporter construct that bears the human IL-15Ralpha promoter, we demonstrated that Tax expression increased promoter activity by at least 4-fold. Furthermore, using promoter deletion constructs and gel shift analysis, we defined a functional NF-kappaB-binding motif in the human IL-15Ralpha promoter, suggesting that Tax activation of IL-15Ralpha is due, in part, to the induction of NF-kappaB. These data indicate that IL-15Ralpha is transcriptionally regulated by the HTLV-I Tax protein through the action of NF-kappaB. These findings suggest a role for IL-15Ralpha in aberrant T cell proliferation observed in HTLV-I-associated diseases.
Mariner
J M
JM
Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. marinerj@mail.nih.gov
Lantz
V
V
Waldmann
T A
TA
Azimi
N
N
D020816:Amino Acid Motifs; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology*; D016356:Gene Products, tax / Q000096:biosynthesis / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000276:immunology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014158:Transcription, Genetic / Q000276:immunology
D016356:Gene Products, tax; C508024:IL15RA protein, human; D019409:Interleukin-15; D016328:NF-kappa B; D012333:RNA, Messenger; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2