Adenovirus E4 open reading frame 4 protein autoregulates E4 transcription by inhibiting E1A transactivation of the E4 promoter
1996 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 70, no 6, 3844-6851 p.Article in journal (Refereed) Published
Here we show that the adenovirus early region 4 (E4) open reading frame 4 (ORF4) protein autoregulates its own transcription by inhibiting adenovirus E1A-induced activation of E4 transcription both in transient transfection experiments and during lytic virus growth. The inhibitory activity of E4-ORF4 was selective for E1A-CR3-dependent transactivation and had no effect on CR1 transactivation. The inhibitory activity of E4-ORF4 was relieved by okadaic acid treatment, which inhibits the cellular protein phosphatase 2A (PP2A), suggesting that E4-ORF4 controls the phosphorylated status of transcription factors important for E4 promoter activity. This conclusion agrees with previous demonstrations that E4-ORF4 associates with PP2A and causes a partial dephosphorylation of certain transcription factors, including E1A (U. Müller, T. Kleinberger, and T. Shenk, J. Virol. 66:5869-5878, 1992; T. Kleinberger and T. Shenk, J. Virol. 67:7556-7560, 1993). However, our results indicate that dephosphorylation of E1A itself might not be the primary target for E4-ORF4. Instead, the E4-ORF4-PP2A complex appears to work by dephosphorylation of multiple cellular transcription factors that are involved in E1A transactivation of the E4 promoter.
Place, publisher, year, edition, pages
1996. Vol. 70, no 6, 3844-6851 p.
IdentifiersURN: urn:nbn:se:uu:diva-52660ISI: A1996UL10400059PubMedID: 8648720OAI: oai:DiVA.org:uu-52660DiVA: diva2:80570