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C/EBP<i>β</i> regulates human immunodeficiency virus 1 gene expression through its association with cdk9

By Giuseppe Mameli, Satish L. Deshmane, Mohammad Ghafouri, Jianqi Cui, Kenneth Simbiri, Kamel Khalili, Ruma Mukerjee, Antonina Dolei, Shohreh Amini and Bassel E. Sawaya

Abstract

Transcriptional regulation of the human immunodeficiency virus type 1 (HIV-1) is a complex event that requires the cooperative action of both viral (<i>e</i>.<i>g</i>. Tat) and cellular (<i>e</i>.<i>g</i>. C/EBP<i>β</i>, NF-<i>κ</i>B) factors. The HIV-1 Tat protein recruits the human positive transcription elongation factor P-TEFb, consisting of cdk9 and cyclin T1, to the HIV-1 transactivation response (TAR) region. In the absence of TAR, Tat activates the HIV-1 long terminal repeat (LTR) through its association with several cellular factors including C/EBP<i>β</i>. C/EBP<i>β</i> is a member of the CCAAT/enhancer-binding protein family of transcription factors and has been shown to be a critical transcriptional regulator of HIV-1 LTR. We examined whether Tat–C/EBP<i>β</i> association requires the presence of the P-TEFb complex. Using immunoprecipitation followed by Western blot, we demonstrated that C/EBP<i>β</i>–cyclin T1 association requires the presence of cdk9. Further, due to its instability, cdk9 was unable to physically interact with C/EBP<i>β</i> in the absence of cyclin T1 or Tat. Using kinase assays, we demonstrated that cdk9, but not a cdk9 dominant-negative mutant (cdk9-dn), phosphorylates C/EBP<i>β</i>. Our functional data show that co-transfection of C/EBP<i>β</i> and cdk9 leads to an increase in HIV-1 gene expression when compared to C/EBP<i>β</i> alone. Addition of C/EBP homologous protein (CHOP) inhibits C/EBP<i>β</i> transcriptional activity in the presence and absence of cdk9 and causes a delay in HIV-1 replication in T-cells. Together, our data suggest that Tat–C/EBP<i>β</i> association is mediated through cdk9, and that phosphorylated C/EBP<i>β</i> may influence AIDS progression by increasing expression of HIV-1 genes

Topics: MED/07 Microbiologia e microbiologia clinica
Publisher: Society for General Microbiology
Year: 2007
OAI identifier: oai:eprints.uniss.it:8549
Provided by: UnissResearch
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