Inhibition of class II trans-activator function by HIV-1 tat in mouse cells is independent of competition for binding to cyclin T1.
The Tat trans-activator protein from HIV-1 inhibits the function of the class II trans-activator protein (CIITA), resulting in reduced MHC class II gene transcription in human cells. Tat does so by competing with CIITA for binding to cyclin T1, a component of the transcriptional elongation complex PTEFb. Since Tat does not functionally interact with mouse cyclin T1, we decided to examine the ability of Tat to inhibit CIITA in mouse cells. We found that Tat inhibited CIITA activity in mouse cells though this inhibition was independent of cyclin T1. The inhibition required the transcriptional activation domain of CIITA, but did not involve alterations in MHC class II promoter occupancy. Although Tat blocked the interaction between CIITA protein and human cyclin T1, it had no effect on the binding between CIITA and mouse cyclin T1. Therefore, Tat can inhibit the ability of CIITA to activate transcription of MHC class II genes in mouse cells by a mechanism that appears to be distinct from that proposed for human cells.
Mudhasani
Rajini
R
Department of Biological, Geological and Environmental Sciences, Cleveland State University, Rm. SI219, Cleveland, OH 44115, USA.
Fontes
Joseph D
JD
D016475:3T3 Cells; D000818:Animals; D001667:Binding, Competitive; D056906:Cyclin T; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000235:genetics* / Q000378:metabolism; D005802:Genes, MHC Class II / Q000235:genetics; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins; D011485:Protein Binding; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
C503684:CCNT1 protein, human; C503685:Ccnt1 protein, mouse; D056906:Cyclin T; D016213:Cyclins; D015696:Gene Products, tat; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D054322:tat Gene Products, Human Immunodeficiency Virus