title: Activation of Tax protein by c-Jun-N-terminal kinase is not dependent on the presence or absence of the early growth response-1 gene product.
abstract: The Tax protein of human T cell leukemia virus type 1 plays a major role in the pathogenesis of adult T cell leukemia (ATL), an aggressive neoplasia of CD4+ T cells. In the present study, we investigated whether the EGR-1 pathway is involved in the regulation of Tax-induced JNK expression in human Jurkat T cells transfected to express the Tax protein in the presence or absence of PMA or ionomycin. Overexpression of EGR-1 in Jurkat cells transfected to express Tax, promoted the activation of several genes, with the most potent being those that contained AP-1 (Jun/c-Fos), whereas knockdown of endogenous EGR-1 by small interfering RNA (siRNA) somewhat reduced Tax-mediated JNK-1 transcription. Additionally, luciferase-based AP-1 and NF-κB reporter gene assays demonstrated that inhibition of EGR-1 expression by an siRNA did not affect the transcriptional activity of a consensus sequence of either AP-1 or NF-κB. On the other hand, the apoptosis assay, using all-trans retinoic acid (ATRA) as an inducer of apoptosis, confirmed that siRNA against EGR-1 failed to suppress ATRA-induced apoptosis in Jurkat and Jurkat-Tax cells, as noted by the low levels of both DEVDase activity and DNA fragmentation, indicating that the induction of apoptosis by ATRA was Egr-1-independent. Finally, our data showed that activation of Tax by JNK-1 was not dependent on the EGR-1 cascade of events, suggesting that EGR-1 is important but not a determinant for the activity for Tax-induced proliferation of Jurkat cells.
authors.affiliation: Laboratory of Experimental Biomedicine, University of Tarapaca, Campus Esmeralda, Iquique, Chile.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Parra
authors.affiliation: Faculty of Sciences, University Arturo Prat, Iquique, Chile.
authors.forename: Luís
authors.initials: L
authors.lastname: Gutierréz
authors.affiliation: Programme of Molecular and Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Santiago, Chile.
authors.forename: Jorge
authors.initials: J
authors.lastname: Ferreira
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002455:Cell Division; D016384:Consensus Sequence; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D048055:Mitogen-Activated Protein Kinase 8 / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000502:physiology; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D016356:Gene Products, tax; D016328:NF-kappa B; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; C514970:tax protein, Human T-lymphotrophic virus 1; D014212:Tretinoin; D048055:Mitogen-Activated Protein Kinase 8; D013755:Tetradecanoylphorbol Acetate