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- W2172051205 abstract "ABSTRACT Human adenovirus type 9 exclusively elicits mammary tumors in experimental animals, and the primary oncogenic determinant of this virus is the E4-ORF1 oncogene, as opposed to the well-known E1A and E1B oncogenes. The tumorigenic potential of E4-ORF1, as well as its ability to oncogenically stimulate phosphatidylinositol 3-kinase (PI3K), depends on a carboxyl-terminal PDZ domain-binding motif (PBM) that mediates interactions with several different membrane-associated cellular PDZ proteins, including MUPP1, PATJ, MAGI-1, ZO-2, and Dlg1. Nevertheless, because certain E4-ORF1 mutations that alter neither the sequence nor the function of the PBM abolish E4-ORF1-induced PI3K activation and cellular transformation, we reasoned that E4-ORF1 must possess an additional crucial protein element. In the present study, we identified seven E4-ORF1 amino acid residues that define this new element, designated domain 2, and showed that it mediates binding to a 70-kDa cellular phosphoprotein. We also discovered that domain 2 or the PBM independently promotes E4-ORF1 localization to cytoplasmic membrane vesicles and that this activity of domain 2 depends on E4-ORF1 trimerization. Consistent with the latter observation, molecular-modeling analyses predicted that E4-ORF1 trimerization brings together six out of seven domain 2 residues at each of the three subunit interfaces. These findings importantly demonstrate that PI3K activation and cellular transformation induced by E4-ORF1 require two separate protein interaction elements, domain 2 and the PBM, each of which targets E4-ORF1 to vesicle membranes in cells." @default.
- W2172051205 created "2016-06-24" @default.
- W2172051205 creator A5033719663 @default.
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- W2172051205 creator A5053738351 @default.
- W2172051205 creator A5080581166 @default.
- W2172051205 date "2007-05-01" @default.
- W2172051205 modified "2023-09-23" @default.
- W2172051205 title "A New Crucial Protein Interaction Element That Targets the Adenovirus E4-ORF1 Oncoprotein to Membrane Vesicles" @default.
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- W2172051205 doi "https://doi.org/10.1128/jvi.02855-06" @default.
- W2172051205 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1900153" @default.
- W2172051205 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17314165" @default.
- W2172051205 hasPublicationYear "2007" @default.
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