Premium
Oncogenic function for the Dlg1 mammalian homolog of the Drosophila discs‐large tumor suppressor
Author(s) -
Frese Kristopher K,
Latorre Isabel J,
Chung SangHyuk,
Caruana Georgina,
Bernstein Alan,
Jones Stephen N,
Donehower Lawrence A,
Justice Monica J,
Garner Craig C,
Javier Ronald T
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601030
Subject(s) - biology , suppressor , drosophila (subgenus) , genetics , function (biology) , microbiology and biotechnology , tumor suppressor gene , gene , carcinogenesis
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.