Extracellular Tat activates c-fos promoter in low serum-starved CD4+ T cells

Davide Gibellini, Maria Carla Re, Cristina Ponti, Claudio Celeghini, Elisabetta Melloni, Michele La Placa, Giorgio Zauli

Research output: Contribution to journalArticle

Abstract

The regulatory human immunodeficiency virus-1 (HIV-1) Tat protein shows pleiotropic effects on the survival and growth of both HIV-1-infected and uninfected CD4+ T lymphocytes. In this study, we have demonstrated that low concentrations (10 ng/ml) of extracellular Tat protein induce the expression of both c-fos mRNA and protein in serum-starved Jurkat CD4+ lymphoblastoid T cells. Using deletion mutants, we demonstrates that the SRE, CRE and, to a lesser extent, also the SIE domains (all placed in the first 356 bp of c-fos promoter) play a key role in mediating the response to extracellular Tat. Moreover, the ability of Tat to activate the transcriptional activity of c-fos promoter was consistently decreased by pretreatment with the ERK/MAPK kinase inhibitor PD98058. Activation of c-fos is functional as demonstrated by induction of the AP-1 transcription factor, which is involved in the regulation of critical genes for the activation of T lymphocytes, such as interleukin 2. The Tat-mediated induction of c-fos and AP-1 in uninfected lymphoid T cells may contribute to explain the immune hyperactivation that characterizes the progression to autoimmuno deficiency syndrome and constitutes the optimal environment for HIV-1 replication, occurring predominantly in activated/proliferating CD4+ T cells.

Original languageEnglish
Pages (from-to)663-670
Number of pages8
JournalBritish Journal of Haematology
Volume112
Issue number3
DOIs
Publication statusPublished - 2001

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Keywords

  • C-fos
  • HIV-1
  • Jurkat
  • MAPKinase
  • Tat

ASJC Scopus subject areas

  • Hematology

Cite this

Gibellini, D., Re, M. C., Ponti, C., Celeghini, C., Melloni, E., La Placa, M., & Zauli, G. (2001). Extracellular Tat activates c-fos promoter in low serum-starved CD4+ T cells. British Journal of Haematology, 112(3), 663-670. https://doi.org/10.1046/j.1365-2141.2001.02576.x