HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator.
The accessory protein, Vpr, is a virion-associated protein that is required for HIV-1 replication in macrophages and regulates viral gene expression in T cells. Vpr causes arrest of cell cycle progression at G2/M, presumably through its effect on cyclin B1.Cdc2 activity. Here, we show that the ability of Vpr to activate HIV transcription correlates with its ability to induce G2/M growth arrest, and this effect is mediated by the p300 transcriptional co-activator, which promotes cooperative interactions between the Rel A subunit of NF-kappaB and cyclin B1.Cdc2. Vpr cooperates with p300, which regulates NF-kappaB and the basal transcriptional machinery, to increase HIV gene expression. Similar effects are seen in the absence of Vpr with a kinase-deficient Cdc2, and overexpression of p300 increases levels of HIV Vpr+ replication. Taken together, these data suggest that p300, through its interactions with NF-kappaB, basal transcriptional components, and Cdks, is modulated by Vpr and regulates HIV replication. The regulation of p300 by Vpr provides a mechanism to enhance viral replication in proliferating cells after growth arrest by increasing viral transcription.
Felzien
L K
LK
Departments of Internal Medicine and Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI 48109-0650, USA.
Woffendin
C
C
Hottiger
M O
MO
Subbramanian
R A
RA
Cohen
E A
EA
Nabel
G J
GJ
D016203:CDC2 Protein Kinase / Q000502:physiology; D050882:CREB-Binding Protein; D002453:Cell Cycle; D015967:Gene Expression Regulation, Viral; D016336:Gene Products, vpr / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D009687:Nuclear Proteins / Q000502:physiology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D054325:vpr Gene Products, Human Immunodeficiency Virus; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D016203:CDC2 Protein Kinase