RGD Reference Report - Oncogenic function for the Dlg1 mammalian homolog of the Drosophila discs-large tumor suppressor. - Rat Genome Database

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Oncogenic function for the Dlg1 mammalian homolog of the Drosophila discs-large tumor suppressor.

Authors: Frese, KK  Latorre, IJ  Chung, SH  Caruana, G  Bernstein, A  Jones, SN  Donehower, LA  Justice, MJ  Garner, CC  Javier, RT 
Citation: Frese KK, etal., EMBO J. 2006 Mar 22;25(6):1406-17. Epub 2006 Mar 2.
RGD ID: 8554336
Pubmed: PMID:16511562   (View Abstract at PubMed)
PMCID: PMC1422156   (View Article at PubMed Central)
DOI: DOI:10.1038/sj.emboj.7601030   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:P890798554336PMID:16511562IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Dlg1  (discs large MAGUK scaffold protein 1)


Additional Information