title: Interaction of CtBP with adenovirus E1A suppresses immortalization of primary epithelial cells and enhances virus replication during productive infection.
abstract: Adenovirus E1A induces cell proliferation, oncogenic transformation and promotes viral replication through interaction with p300/CBP, TRRAP/p400 multi-protein complex and the retinoblastoma (pRb) family proteins through distinct domains in the E1A N-terminal region. The C-terminal region of E1A suppresses E1A/Ras co-transformation and interacts with FOXK1/K2, DYRK1A/1B/HAN11 and CtBP1/2 (CtBP) protein complexes. To specifically dissect the role of CtBP interaction with E1A, we engineered a mutation (DL→AS) within the CtBP-binding motif, PLDLS, and investigated the effect of the mutation on immortalization and Ras cooperative transformation of primary cells and viral replication. Our results suggest that CtBP-E1A interaction suppresses immortalization and Ras co-operative transformation of primary rodent epithelial cells without significantly influencing the tumorigenic activities of transformed cells in immunodeficient and immunocompetent animals. During productive infection, CtBP-E1A interaction enhances viral replication in human cells. Between the two CtBP family proteins, CtBP2 appears to restrict viral replication more than CtBP1 in human cells.
authors.affiliation: Institute for Molecular Virology, Saint Louis University Health Sciences Center, Doisy Research Center, 1100 South Grand Blvd., Saint Louis, MO 63104, USA.
authors.forename: T
authors.initials: T
authors.lastname: Subramanian
authors.forename: Ling-Jun
authors.initials: LJ
authors.lastname: Zhao
authors.forename: G
authors.initials: G
authors.lastname: Chinnadurai
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D011905:Genes, ras; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D011485:Protein Binding; D051381:Rats; D014779:Virus Replication
chemical_list: D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein
keywords: CtBP interaction; HAdv5 E1A; Immortalization; Ras co-transformation; Virus replication