Activation of the JC virus Tat-responsive transcriptional control element by association of the Tat protein of human immunodeficiency virus 1 with cellular protein Pur alpha.
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 Pur alpha, 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 Pur alpha to form a complex that can be immunoprecipitated from cell extracts. Tat enhances the ability of purified glutathione S-transferase-Pur alpha (GST-Pur alpha) to bind the upTAR element. Tat acts synergistically with Pur alpha, in a cell-cycle-dependent manner, to activate transcription at an upTAR element placed upstream of a heterologous promoter. Since Pur alpha is ubiquitously expressed in human cells and since PUR elements are located near many promoters and origins of replication, the Tat-Pur alpha interaction may be implicated in effects of HIV-1 throughout the full range of HIV-1-infected cells.
Krachmarov
C P
CP
Department of Pathology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Chepenik
L G
LG
Barr-Vagell
S
S
Khalili
K
K
Johnson
E M
EM
D000595:Amino Acid Sequence; D001665:Binding Sites; D002453:Cell Cycle; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D017362:Cyclic AMP Response Element-Binding Protein; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D015696:Gene Products, tat / Q000302:isolation & purification / Q000378:metabolism*; D005909:Glioblastoma; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007577:JC Virus / Q000502:physiology*; D007930:Leucine; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000502:physiology* / Q000821:virology*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D014775:Virus Activation; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D015696:Gene Products, tat; C501130:PURA protein, human; D011994:Recombinant Proteins; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D015500:Chloramphenicol O-Acetyltransferase; D007930:Leucine