title: Growth inhibition of Tax-activated human Jurkat leukemia T cells by             all-trans retinoic acid requires JNK-1 inhibition.
abstract: Retinoids, including vitamin A (retinol) and its analogues, are critical             for a variety of biological functions. In this study, we report that all-trans             retinoic acid (ATRA) decreases Jun N-terminal kinase 1 (JNK-1) activity, antagonizing             the effect of the Tax protein in Jurkat leukemia T cells transiently transfected             for expressing the Tax protein. The Tax protein is one of the products of the             human T-cell leukemia virus type 1 (HTLV-1) which is the etiologic agent of adult             T-cell leukemia (ATL), an aggressive neoplasia of CD4+ T cells. The decrease in             JNK-1 activity was followed by a marked decrease in the expression of interleukin             (IL)-2 and a weak increase in interferon (IFN)-γ in Jurkat cells treated with             ATRA in a dose-dependent manner, suggesting a correlation between the expression             of JNK-1 and the activity of the Tax protein. However, the expression levels of             IL-4 and IL-10 were enhanced in cells transfected with Tax, compared with the             levels in untransfected cells, but the expression levels were not affected following             ATRA treatment. In transfection studies using a luciferase reporter construct             expressing the IL-2 promoter or a tandem repeat of AP-1 or NF-κB, the inhibitory             effect of ATRA on the IL-2 promoter and AP-1 construct was confirmed at the transcriptional             level. However, the inhibitory effect in the NF-κB reporter construct was only             marginal. In addition, our data demonstrated that JNK-1 is constitutively activated             in Jurkat leukemia T cells expressing the Tax protein, suggesting that JNK-1 is             required for Tax-induced proliferation of Jurkat leukemia cells.
authors.affiliation: Biomedical Experimental Laboratory, Faculty of Sciences, University of Tarapaca, Arica, Chile. eparra@uta.cl
authors.forename: Eduardo
authors.initials: E
authors.lastname: Parra
authors.forename: Luis
authors.initials: L
authors.lastname: Gutiérrez
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D016356:Gene Products, tax / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008156:Luciferases / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016356:Gene Products, tax; D007376:Interleukin-2; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D016753:Interleukin-10; D015847:Interleukin-4; D014212:Tretinoin; D007371:Interferon-gamma; D008156:Luciferases; D048055:Mitogen-Activated Protein Kinase 8; D010447:Peptide Hydrolases; C108711:DEVDase