Activation of the JC Virus Tat-Responsive Transcriptional Control Element by Association of the Tat Protein of Human Immunodeficiency Virus 1 with Cellular Protein Purα

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 93; no. 24; pp. 14112 - 14117
• Main Authors: Krachmarov, Chavdar P., Chepenik, Lara G., Barr-Vagell, Sharon, Khalili, Kamel, Johnson, Edward M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 26-11-1996; National Acad Sciences; The National Academy of Sciences
• Subjects: AIDS/HIV; Amino Acid Sequence; Antibodies; Binding Sites; Biological Sciences; Cell Cycle; Cell Line; Cell lines; Chloramphenicol O-Acetyltransferase - biosynthesis; Cyclic AMP Response Element-Binding Protein; DNA; DNA Replication; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; Gels; Gene Products, tat - isolation & purification; Gene Products, tat - metabolism; Glioblastoma; HIV 1; HIV-1 - physiology; human immunodeficiency virus 1; Humans; JC virus; JC Virus - physiology; Leucine; Molecular Sequence Data; Neuroglia; Neuroglia - physiology; Neuroglia - virology; Oligonucleotides; Plasmids; Protein Binding; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Sequence Deletion; Sequence Homology, Amino Acid; tat Gene Products, Human Immunodeficiency Virus; Transcription Factors; Transcription, Genetic; Transfection; Virus Activation; Virus Replication
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.24.14112

JC virus is activated to replicate in glial cells of many AIDS patients with neurological disorders. In human glial cells, the human immunodeficiency virus 1 (HIV-1) Tat protein activates the major late promoter of JC virus through a Tat-responsive DNA element, termed upTAR, which is a recognition site for cellular Purα , a sequence-specific single-stranded DNA binding protein implicated in cell cycle control of DNA replication and transcription. Tat interacts with two leucine-rich repeats in Purα to form a complex that can be immunoprecipitated from cell extracts. Tat enhances the ability of purified glutathione S-transferase-Purα (GST-Purα ) to bind the upTAR element. Tat acts synergistically with Purα , in a cell-cycle-dependent manner, to activate transcription at an upTAR element placed upstream of a heterologous promoter. Since Purα is ubiquitously expressed in human cells and since PUR elements are located near many promoters and origins of replication, the Tat-Purα interaction may be implicated in effects of HIV-1 throughout the full range of HIV-1-infected cells.