title: Adenovirus E4 open reading frame 4 protein autoregulates E4 transcription by inhibiting E1A transactivation of the E4 promoter.
abstract: 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.
authors.affiliation: Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Bondesson
authors.forename: K
authors.initials: K
authors.lastname: Ohman
authors.forename: M
authors.initials: M
authors.lastname: Manervik
authors.forename: S
authors.initials: S
authors.lastname: Fan
authors.forename: G
authors.initials: G
authors.lastname: Akusjärvi
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D017500:Adenovirus E1A Proteins / Q000502:physiology*; D001483:Base Sequence; D004988:Ethers, Cyclic / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral; D006706:Homeostasis; D008969:Molecular Sequence Data; D019319:Okadaic Acid; D016366:Open Reading Frames; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D017500:Adenovirus E1A Proteins; D004988:Ethers, Cyclic; D012333:RNA, Messenger; D019319:Okadaic Acid