Adenovirus E4-34kDa requires active proteasomes to promote late gene expression

• Published in: Virology (New York, N.Y.) N.Y.), 2003-10, Vol.315 (1), p.234-244
• Main Authors: Corbin-Lickfett, Kara A, Bridge, Eileen
• Format: Article
• Language: English
• Subjects: 26S proteasome; Acetylcysteine - analogs & derivatives; Acetylcysteine - pharmacology; Adenovirus; Adenovirus E4 Proteins - genetics; Adenovirus E4 Proteins - metabolism; Adenoviruses, Human - genetics; Adenoviruses, Human - physiology; Animals; Cell Line; Cercopithecus aethiops; E1b-55kDa; E4 ORF3; E4 ORF6; E4-11kDa; E4-34kDa; Gene Expression Regulation, Viral; Genetic Complementation Test; HeLa Cells; Humans; Lactacystin; MG132; Mutation; Peptide Hydrolases - metabolism; Proteasome Endopeptidase Complex; Virus Replication
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/S0042-6822(03)00527-0

A complex of the Adenovirus (Ad) early region 1b 55-kDa protein (E1b-55kDa) and the early region 4 ORF6 34-kDa protein (E4-34kDa) promotes viral late RNA accumulation in the cytoplasm while inhibiting the transport of most newly synthesized cellular mRNA. The E4 ORF3 11-kDa protein (E4-11kDa) functionally compensates for at least some of the activities of this complex. We find that the same large central region of E4-34kDa that is required for proteasome-mediated degradation of p53 (J. Virol. 75, (2001) 699–709) is also required to promote viral late gene expression in a complementation assay. E4-34kDa does not promote late gene expression in complementation assays performed in the presence of proteasome inhibitors. A proteasome inhibitor also dramatically reduced late gene expression by a virus that lacks the E4-11kDa gene and therefore relies on E4-34kDa for late gene expression. Our results suggest that E4-34kDa activity in promoting late gene expression depends on the proteasome.