Interaction between cell cycle regulator, E2F-1, and NF-kappa B mediates repression of HIV-1 gene transcription

被引:41
作者
Kundu, M
Guermah, M
Roeder, RG
Amini, S
Khalili, K
机构
[1] ALLEGHENY UNIV HLTH SCI,CTR NEUROVIROL & NEUROONCOL,PHILADELPHIA,PA 19102
[2] ALLEGHENY UNIV HLTH SCI,DEPT NEUROL,PHILADELPHIA,PA 19102
[3] ROCKEFELLER UNIV,BIOCHEM & MOL BIOL LAB,NEW YORK,NY 10021
关键词
D O I
10.1074/jbc.272.47.29468
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The NF-kappa E/Rel family of transcription factors is one of the main targets of cytokines and other agents that induce HIV-1 gene expression, Some of these extracellular stimuli arrest cells in the G(1) phase of the mitotic division cycle and modulate the activity of the tumor suppressor protein Rb and its partner E2F-1, Earlier studies indicated that E2F-1, a transcription factor that stimulates expression of S phase-specific genes, is able to repress transcription directed by the human immunodeficiency virus (HIV-1) type-1 promoter in a variety of cells, including those of glial and lymphocytic origin, Here, we demonstrate that E2F-1 may regulate the activity of the HIV-1 long terminal repeat through its ability to bind sequences in the NF-kappa B enhancer region and to interact with the NF-kappa B subunit, p50, Gel retardation and methylation interference assays show that E2F-1 is able to bind specifically to a site embedded within the two NF-kappa B elements, Gel retardation/immunoblot analysis using purified E2F-1 and p50 homodimers reveals the presence of complexes containing both proteins, Affinity chromatography and co-immunoprecipitation assays provide evidence for direct interaction of E2F-1 and p50 in the absence of their DNA target sequences, In vitro transcription assay demonstrates that E2F-1 represses NF-kappa B mediated transcription in a cell-free system, Functional studies in Jurkat T lymphocytic cells point to the importance of both the E2F and NF-kappa B binding sites in E2F-1 mediated repression of HIV-1 promoter, in vivo. The results of this study suggest that NF-kappa B activity may be regulated by its interaction with the cell cycle regulatory protein, E2F-1.
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页码:29468 / 29474
页数:7
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