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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
Author(s) -
Rohr Olivier,
Schwartz Christian,
Aunis Dominique,
Schaeffer Evelyne
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19991201)75:3<404::aid-jcb6>3.0.co;2-g
Subject(s) - creb , transactivation , creb1 , jurkat cells , transcription factor , response element , long terminal repeat , biology , microbiology and biotechnology , transcription (linguistics) , cyclic amp response element binding protein , gene , promoter , gene expression , genetics , t cell , linguistics , immune system , philosophy
Abstract 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/+80 and ‐68/+80 LTR region, respectively. We have previously demonstrated that COUP‐TF stimulates HIV‐1 transcription via the ‐68/+29 LTR region without direct DNA binding. Here, gel supershift experiments show that CREB does not directly bind to the ‐45/+85 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/+80 LTR region, through the transcription factors CREB and COUP‐TF. J. Cell. Biochem. 75:404–413, 1999. © 1999 Wiley‐Liss, Inc.