Transcription factor TFIIH components enhance the GR coactivator activity but not the cell cycle-arresting activity of the human immunodeficiency virus type-1 protein Vpr.
The human immunodeficiency virus type-1 (HIV-1)-accessory protein Vpr interacts with and potentiates the activity of the glucocorticoid receptor (GR) and arrests the host cell cycle at the G2/M boundary. Here we report that three core components of the general transcription factor (TF) IIH, CDK7, Cyclin H, and MAT1, enhance Vpr's GR coactivator activity but inhibit its cell cycle-arresting function. A CDK7 mutant defective in kinase activity for the C-terminal tail of RNA polymerase II, which cannot form a functional TFIIH complex, did not enhance Vpr coactivator activity. Overexpression of all three TFIIH components and p300 cooperatively enhanced Vpr coactivator activity, whereas TFIIH overexpression did not potentiate the transcriptional activity of a Vpr mutant, which does not bind p300/CBP. These findings suggest that TFIIH participates in Vpr's GR coactivating activity, at a step beyond its interaction with p300/CBP.
Kino
Tomoshige
T
Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. kinot@mail.nih.gov
Tsukamoto
Makoto
M
Chrousos
George
G
D001665:Binding Sites; D002453:Cell Cycle; D056748:Cyclin H; D018844:Cyclin-Dependent Kinases / Q000502:physiology; D016213:Cyclins / Q000502:physiology; D016336:Gene Products, vpr / Q000494:pharmacology*; D015497:HIV-1; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D009363:Neoplasm Proteins / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D051758:Transcription Factor TFIIH; D019473:Transcription Factors, TFII / Q000737:chemistry / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D054325:vpr Gene Products, Human Immunodeficiency Virus; D000095043:Cyclin-Dependent Kinase-Activating Kinase
C534751:CCNH protein, human; D056748:Cyclin H; D016213:Cyclins; D016336:Gene Products, vpr; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011965:Receptors, Glucocorticoid; D015534:Trans-Activators; D019473:Transcription Factors, TFII; D054325:vpr Gene Products, Human Immunodeficiency Virus; D051758:Transcription Factor TFIIH; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase