HIV-1 Tat interaction with cyclin T1 represses mannose receptor and the bone morphogenetic protein receptor-2 transcription.
Macrophage transcription is significantly altered by HIV-1 infection. HIV Tat, an immediate-early product of the viral lifecycle, interacts with host transcription factors to alter host gene expression. We have previously shown that Tat represses transcription from the mannose receptor (MR) and the bone morphogenetic protein receptor-2 (BMPR2) promoters. The current study shows that transcriptional repression of these receptors involves Tat interaction with cyclin T1. Assays using U937 human monocytic cells transiently expressing MR or BMPR2 promoter-luciferase constructs demonstrated equal repression by one- and two-exon Tat gene products. A mutant Tat expression vector encoding Tat protein lacking the cyclin T1 binding domain failed to inhibit MR and BMPR2 promoter activities. Over-expression of cyclin T1 in the presence of wild-type Tat resulted in recovered activity from both promoters. Finally, two inhibitors of cyclin-dependent kinase 9 (a dominant negative CDK9 and flavopiridol) repressed activity from the MR and BMPR2 promoters.
Caldwell
Robert L
RL
Department of Pathology, Vanderbilt University School of Medicine, Veterans Affairs Medical Center, Nashville, TN, USA.
Lane
Kirk B
KB
Shepherd
Virginia L
VL
D001665:Binding Sites; D055396:Bone Morphogenetic Protein 2; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D056906:Cyclin T; D016213:Cyclins / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D000074443:Lysine Acetyltransferase 5; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C503684:CCNT1 protein, human; D056906:Cyclin T; D016213:Cyclins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II