We are currently conducting clinical trials of E1A gene therapy for patients with ovarian cancer. The adenovirus type 5 E1A gene suppresses growth of ovarian cancer cells that overexpress HER-2/neu (HER2) and growth of some--but not all--that express low HER2. In HER2-overexpressing cells, suppression by E1A is predominantly by down-regulation of HER2, but the mechanism in low HER2-expressing c...

The adenovirus (Ad) E1A (Ad-E1A) oncoprotein mediates cell transformation, in part, by displacing E2F transcription factors from the retinoblastoma protein (pRb) tumor suppressor. In this study we determined the crystal structure of the pRb pocket domain in complex with conserved region 1 (CR1) of Ad5-E1A. The structure and accompanying biochemical studies reveal that E1A-CR1 binds at the inter...

Adenovirus e1a induces quiescent human cells to replicate. We found that e1a causes global relocalization of the RB (retinoblastoma) proteins (RB, p130, and p107) and p300/CBP histone acetyltransferases on promoters, the effect of which is to restrict the acetylation of histone 3 lysine-18 (H3K18ac) to a limited set of genes, thereby stimulating cell cycling and inhibiting antiviral responses a...

The expression of the Adenovirus serotype 2 or serotype 5 (Ad2/5) E1A gene in tumor cells upregulates ligands that are recognized by the NKG2D activating receptor, which is expressed on NK cells and T cells, and reduces their tumorigenicity, a process dependent on NK cells and T cells. In some model systems, the forced overexpression of NKG2D ligands on tumor cells induced antigen-specific CD8+...

Expression of the adenoviral E1A oncogene induces susceptibility of neoplastic cells from different species to both immune-mediated and chemotherapy-induced cell death. These effects of E1A are easily measured in vitro using cytotoxicity assays. However, conventional in vivo assays of tumor development lack similar precision for measurement of oncogene-induced changes in tumor cell traits. E1A ...

We focused on the regulation of inflammatory mediator expression by adenovirus E1A in lung epithelial cells and the role of this viral protein in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously reported that E1A, a well-known regulator of host genes, increased ICAM-1 expression in human bronchial epithelial (HBE) and A549 cells in response to LPS stimulation. In ...

The oncoproteins of the small DNA tumor viruses interact with a plethora of cellular regulators to commandeer control of the infected cell. During infection, adenovirus E1A deregulates cAMP signalling and repurposes it for activation of viral gene expression. We show that E1A structurally and functionally mimics a cellular A-kinase anchoring protein (AKAP). E1A interacts with and relocalizes pr...

Rat 3Y1 fibroblasts transformed by the E1A gene of adenovirus type 12 (E1A-3Y1 cells) are highly sensitive to the cell-killing effect of 1,3-dilinoleoylglycerol (DLG) administered in a culture medium, whereas the parental 3Y1 cells are less sensitive (H. Shimura et al., Cancer Res., 48: 578-583, 1988). The selective cytotoxicity of DLG to E1A-3Y1 cells was markedly reduced by the simultaneous a...

Upon infection, human adenovirus (HAdV) must activate the expression of its early genes to reprogram the cellular environment to support virus replication. This activation is orchestrated in large part by the first HAdV gene expressed during infection, early region 1A (E1A). E1A binds and appropriates components of the cellular transcriptional machinery to modulate cellular gene transcription a...

The Ad5 E1A database is a listing of mutations affecting the early region 1A (E1A) proteins of human adenovirus type 5. The database contains the name of the mutation, the nucleic acid sequence changes, the resulting alterations in amino acid sequence and reference. Additional notes and references are provided on the effect of each mutation on E1A function. The database is contained within the ...