Distinct domains of adenovirus E1A interact with specific cellular factors to differentially modulate human immunodeficiency virus transcription

Scott F. Parker, Lisa K. Felzien, Neil D. Perkins, Michael J. Imperiale, Gary J. Nabel

Research output: Contribution to journalArticle

Abstract

Transcription of human immunodeficiency virus (HIV) type 1 and other viruses is regulated by the transcription factor NF-κB, which interacts with the multifunctional cellular protein p300. p300, originally identified by its ability to bind adenovirus early region 1A (E1A), has also been shown to regulate HIV transcription through its interaction with NF-κB. The 13S form of E1A activates HIV gene expression, while the 12S form represses its transcription. In this report, we have investigated whether these divergent effects of E1A are dependent upon common or distinct cellular cofactors, including p300, pRb, and the TATA box-binding protein (TBP). Unlike activation in the absence of E1A, cooperative stimulation of HIV gene expression by 13S E1A and RelA was independent of the ability of E1A to bind p300 but was critically dependent on the E1A CR3 region which associates with TBP. In contrast, inhibition of basal HIV gene expression by the 12S form of E1A was dependent on p300 but not pRb or TBP. Interestingly, mutation of the CR2 region of 12S E1A responsible for pRb binding abolished the repression of HIV transcription stimulated by tumor necrosis factor alpha, suggesting that repression of cytokine-activated transcription involves cofactors different from those used in unstimulated cells. Repression and activation of HIV transcription by different forms of E1A are mediated by distinct sets of cellular cofactors. These findings suggest that E1A has evolved to interact by alternative mechanisms with a transcriptional coactivator and its associated cofactors to differentially modulate cellular and viral gene expression.

Original languageEnglish (US)
Pages (from-to)2004-2012
Number of pages9
JournalJournal of Virology
Volume71
Issue number3
StatePublished - Mar 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Parker, S. F., Felzien, L. K., Perkins, N. D., Imperiale, M. J., & Nabel, G. J. (1997). Distinct domains of adenovirus E1A interact with specific cellular factors to differentially modulate human immunodeficiency virus transcription. Journal of Virology, 71(3), 2004-2012.