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Transcriptional regulation of the chemokine co-receptor CCR5 by the cAMP/PKA/CREB pathway
Journal article   Open access   Peer reviewed

Transcriptional regulation of the chemokine co-receptor CCR5 by the cAMP/PKA/CREB pathway

Anupam Banerjee, Vanessa Pirrone, Brian Wigdahl and Michael R Nonnemacher
Biomedicine & pharmacotherapy, v 65(4), pp 293-297
Jul 2011
DOI: https://doi.org/10.1016/j.biopha.2011.03.009
PMID: 21719243
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1016/j.biopha.2011.03.009View
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Abstract

Cell Nucleus - immunology Stem Cells - immunology Transcription, Genetic - drug effects HIV-1 - pathogenicity Phosphorylation Humans Receptors, CCR5 - genetics HIV Core Protein p24 Stem Cells - metabolism Cyclic AMP - physiology Bone Marrow Cells - virology Cell Nucleus - metabolism Isoquinolines - pharmacology Antigens, CD34 - immunology Bone Marrow Cells - immunology Cell Culture Techniques Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors Cyclic AMP - metabolism RNA - metabolism Cyclic AMP-Dependent Protein Kinases - metabolism Stem Cells - virology CD4 Antigens - immunology Cell Line Colforsin - pharmacology Reverse Transcriptase Polymerase Chain Reaction Sulfonamides - pharmacology Cyclic AMP Response Element-Binding Protein - physiology Blotting, Western Cyclic AMP-Dependent Protein Kinases - physiology Signal Transduction - drug effects Cyclic AMP Response Element-Binding Protein - metabolism Protein Kinase Inhibitors - pharmacology Bone Marrow Cells - metabolism
The cyclic adenosine monophosphate (cAMP)-dependent signaling pathway directs the expression of several genes involved in diverse neuroendocrine, immune, metabolic, and developmental pathways. The primary effectors of this pathway are members of the cAMP response element binding (CREB) family of transcription factors, in particular the CREB-1 and cAMP response element modulator (CREM). Both these genes encode alternative splice variants that serve as activators or repressors in a context- and position-specific manner. Although the β-chemokine receptor CC chemokine receptor 5 (CCR5) has been identified on progenitor cells in the bone marrow, the regulatory mechanisms orchestrating its expression are not fully understood. Previous reports have identified putative cAMP response elements in the CCR5 promoter and have described a suppressive role of cAMP in CCR5 expression. In this study, the CD34+CD4+CCR5+ human bone marrow progenitor cell line TF-1 was used to investigate the detailed kinetics of CCR5 transcription in response to the elevation of intracellular cAMP levels and the underlying molecular events. We hypothesize that CCR5 transcription follows an asymmetrical sinusoidal pattern in TF-1 cells that parallels a protein kinase A-dependent alternating change in the ratio of activator pCREB-1-α,Δ to repressor pCREM-α,β isoforms. However, elevated CCR5 mRNA levels do not correlate with enhancement in infectivity with respect to the R5 human immunodeficiency virus type 1 (HIV-1) strain. Our results lend critical insight into the precise mechanism governing the cAMP-CCR5 axis in progenitor cells and pose interesting questions regarding its functional role in HIV-1 infection.

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Web of Science research areas
Medicine, Research & Experimental
Pharmacology & Pharmacy
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