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Extracellular Tat activates c-fos promoter in low serum-starved CD4+ T cells.
- Source :
-
British Journal of Haematology . Mar2001, Vol. 112 Issue 3, p663-670. 8p. 2 Diagrams, 6 Graphs, 1 Map. - Publication Year :
- 2001
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HIV
*T cells
*MESSENGER RNA
Subjects
Details
- Language :
- English
- ISSN :
- 00071048
- Volume :
- 112
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- British Journal of Haematology
- Publication Type :
- Academic Journal
- Accession number :
- 6216979
- Full Text :
- https://doi.org/10.1046/j.1365-2141.2001.02576.x