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Human immunodeficiency virus type-1 tat enhances interleukin-2 promoter activity through synergism with phorbol ester and calcium-mediated activation of the NF-AT cis-regulatory motif.

Abstract
Interference with T cell activation signals by Human immunodeficiency virus (HIV) gene products is suggested to contribute to the impairment of immune functions observed in AIDS. Interleukin-2 (IL-2) and HIV share common stimulatory signals triggered during T cell activation. The role of HIV tat, which is the main enhancing factor for viral LTR, in the regulation of IL-2 gene transcription has been studied following transient expression of the tat gene in phorbol ester and calcium ionophore-activated Jurkat cells transfected with IL-2 promoter-chloramphenicol acetyltransferase reporter constructs. We observed that tat increased the IL-2 promoter transcriptional activity in response to phorbol ester and ionomycin. This tat-dependent synergism mapped to the (-279 to -263 bp) NFAT motif of the IL-2 enhancer, which was sufficient to be transactivated by tat. Our data suggest that tat links T cell activating signals to the shared IL-2 and HIV regulation. This may play a role in the early phase of HIV infection.
AuthorsA Vacca, M Farina, M Maroder, E Alesse, I Screpanti, L Frati, A Gulino
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 205 Issue 1 Pg. 467-74 (Nov 30 1994) ISSN: 0006-291X [Print] United States
PMID7999066 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA-Binding Proteins
  • Gene Products, tat
  • Interleukin-2
  • NFATC Transcription Factors
  • NFATC3 protein, human
  • NFATC4 protein, human
  • Nuclear Proteins
  • Transcription Factors
  • tat Gene Products, Human Immunodeficiency Virus
  • Tetradecanoylphorbol Acetate
  • Calcium
Topics
  • Calcium (pharmacology)
  • Cell Line
  • DNA-Binding Proteins (genetics, metabolism)
  • Enhancer Elements, Genetic
  • Gene Products, tat (physiology)
  • HIV-1 (genetics)
  • Humans
  • Interleukin-2 (genetics)
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Promoter Regions, Genetic
  • Regulatory Sequences, Nucleic Acid
  • Tetradecanoylphorbol Acetate (pharmacology)
  • Transcription Factors (genetics, metabolism)
  • Transcription, Genetic
  • Up-Regulation
  • tat Gene Products, Human Immunodeficiency Virus

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