Adenovirus E4-34kDa requires active proteasomes to promote late gene expression.
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.
Department of Microbiology, 32 Pearson Hall, Miami University, Oxford, OH 45056, USA.
Kara A
KA
Corbin-Lickfett
Eileen
E
Bridge
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017504:Adenovirus E4 Proteins / Q000235:genetics / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D010447:Peptide Hydrolases / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D014779:Virus Replication
D017504:Adenovirus E4 Proteins; C067713:lactacystin; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D000111:Acetylcysteine