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- Title
Oncogenic function for the Dlg1 mammalian homolog of the Drosophila discs-large tumor suppressor.
- Authors
Frese, Kristopher K; Latorre, Isabel J; Chung, Sang-Hyuk; Caruana, Georgina; Bernstein, Alan; Jones, Stephen N; Donehower, Lawrence A; Justice, Monica J; Garner, Craig C; Javier, Ronald T
- Abstract
The fact that several different human virus oncoproteins, including adenovirus type 9 E4-ORF1, evolved to target the Dlg1 mammalian homolog of the membrane-associated Drosophila discs-large tumor suppressor has implicated this cellular factor in human cancer. Despite a general belief that such interactions function solely to inactivate this suspected human tumor suppressor protein, we demonstrate here that E4-ORF1 specifically requires endogenous Dlg1 to provoke oncogenic activation of phosphatidylinositol 3-kinase (PI3K) in cells. Based on our results, we propose a model wherein E4-ORF1 binding to Dlg1 triggers the resulting complex to translocate to the plasma membrane and, at this site, to promote Ras-mediated PI3K activation. These findings establish the first known function for Dlg1 in virus-mediated cellular transformation and also surprisingly expose a previously unrecognized oncogenic activity encoded by this suspected cellular tumor suppressor gene.
- Publication
The EMBO journal, 2006, Vol 25, Issue 6, p1406
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1038/sj.emboj.7601030