Transcriptional regulation of human polyomavirus JC: Evidence for a functional interaction between RelA (p65) and the Y-box-binding protein, YB- 1

Ganesh V. Raj, Mahmut Safak, Gene H. Macdonald, Kamel Khalili

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Abstract

The transcriptional control region of the human neurotropic polyomavirus JC virus contains a consensus NF-κB site which has been shown to enhance both basal and extracellular stimulus-induced levels of transcription of JC promoters. Here, we show that the expression of JC late promoter constructs containing the NF-κB site is decreased by cotransfection with the NF-κB/rel subunits, p50 and p52, but enhanced by the p65 subunit. However, JC promoter constructs lacking the NF-κB site were activated by p52 and p50 and repressed by p65. This antithetical response of the JC promoter mapped specifically to the D domain, which is a target site for the cellular transcription factor, YB-1. Band shift studies indicated that YB-1 and p65 modulate each other's binding to DNA: YB-1 augments the affinity of p65 for the NF-κB site, while p65 reduces the binding of YB-1 to the D domain. Results from coimmunoprecipitation followed by Western blot (immunoblot) analysis suggest an in vivo interaction between p65 and YB-1 in glial cells. Functionally, YB-1 appears to act synergistically with p65 to control transcription from the NF-κB site. A converse pattern is seen with the D domain, in which YB-1 acts synergistically with p50 and p52 to regulate transcription. p50 and p52 may function as transcriptional activators on the D domain by removing the repressive effect of p65 on YB-1 binding to the D domain. On the basis of these data, we propose a model in which NF-κB/rel subunits functionally interact with consensus NF-κB sites or YB-1-binding sites, with disparate effects on eukaryotic gene expression.

Original languageEnglish (US)
Pages (from-to)5944-5953
Number of pages10
JournalJournal of Virology
Volume70
Issue number9
StatePublished - Sep 1996

Fingerprint

Y-Box-Binding Protein 1
JC polyomavirus
JC Virus
binding proteins
Western Blotting
promoter regions
transcription (genetics)
Neuroglia
Transcription Factors
Binding Sites
Gene Expression
DNA
neuroglia
binding sites
Western blotting
transcription factors
gene expression

ASJC Scopus subject areas

  • Immunology

Cite this

Transcriptional regulation of human polyomavirus JC : Evidence for a functional interaction between RelA (p65) and the Y-box-binding protein, YB- 1. / Raj, Ganesh V.; Safak, Mahmut; Macdonald, Gene H.; Khalili, Kamel.

In: Journal of Virology, Vol. 70, No. 9, 09.1996, p. 5944-5953.

Research output: Contribution to journalArticle

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abstract = "The transcriptional control region of the human neurotropic polyomavirus JC virus contains a consensus NF-κB site which has been shown to enhance both basal and extracellular stimulus-induced levels of transcription of JC promoters. Here, we show that the expression of JC late promoter constructs containing the NF-κB site is decreased by cotransfection with the NF-κB/rel subunits, p50 and p52, but enhanced by the p65 subunit. However, JC promoter constructs lacking the NF-κB site were activated by p52 and p50 and repressed by p65. This antithetical response of the JC promoter mapped specifically to the D domain, which is a target site for the cellular transcription factor, YB-1. Band shift studies indicated that YB-1 and p65 modulate each other's binding to DNA: YB-1 augments the affinity of p65 for the NF-κB site, while p65 reduces the binding of YB-1 to the D domain. Results from coimmunoprecipitation followed by Western blot (immunoblot) analysis suggest an in vivo interaction between p65 and YB-1 in glial cells. Functionally, YB-1 appears to act synergistically with p65 to control transcription from the NF-κB site. A converse pattern is seen with the D domain, in which YB-1 acts synergistically with p50 and p52 to regulate transcription. p50 and p52 may function as transcriptional activators on the D domain by removing the repressive effect of p65 on YB-1 binding to the D domain. On the basis of these data, we propose a model in which NF-κB/rel subunits functionally interact with consensus NF-κB sites or YB-1-binding sites, with disparate effects on eukaryotic gene expression.",
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