CREB and COUP-tF mediate transcriptional activation of the human immunodeficiency virus type 1 genome in jurkat t cells in response to cyclic AMP and dopamine
✍ Scribed by Olivier Rohr; Christian Schwartz; Dominique Aunis; Evelyne Schaeffer
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 236 KB
- Volume
- 75
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Infection of lymphocytes by the human immunodeficiency virus type 1 (HIV-1) is associated with an increase in intracellular cAMP levels. Recent studies have shown that lymphocytes are able to synthesize and bind the dopamine, known to affect multiple cellular pathways, such as the cAMP pathway. Here we have investigated the molecular mechanisms by which cAMP and dopamine regulate HIV-1 gene transcription in Jurkat T cells. Transient expression experiments revealed that dopamine and forskolin lead to a synergistic stimulation of long terminal repeat (LTR)-driven transcription. This action is mediated through the cAMP response element binding (CREB) protein and chicken ovalbumin upstream promoter transcription factor (COUP-TF). CREB and COUP-TF act indirectly through the minimal -40/ϩ80 and -68/ϩ80 LTR region, respectively. We have previously demonstrated that COUP-TF stimulates HIV-1 transcription via the -68/ϩ29 LTR region without direct DNA binding. Here, gel supershift experiments show that CREB does not directly bind to the -45/ϩ85 proximal LTR sequences. Moreover, our data reveal novel functional interactions between COUP-TF and CREB, which lead to synergistic cAMP-and dopamine-induced transactivation of the HIV-1 LTR. These findings reveal that dopamine-induced signals and the cAMP pathway stimulate HIV-1 gene transcription in lymphocytes by converging to the minimal -68/ϩ80 LTR region, through the transcription factors CREB and COUP-TF.