The adenovirus E1A-243R protein has the ability to force a resting cell into uncontrolled proliferation by modulating the activity of key targets in cell cycle control. Most of these regulatory mechanisms are dependent on activities mapping to conserved region 1 (CR1) and the non-conserved N-terminal region of E1A. We have previously shown that CR1 functions as a very patent transactivator when...

A spontaneous variant of adenovirus (Ad) type 3 (subgroup B) was identified, which did not grow in HeLa cells, but grew in 293 cells with a large plaque morphology. The variant (Ad3var100) had a defect in the the early gene region E1a; it could grow in cells that supplied E1a functions and was complemented for growth in HeLa cells by Ad5 wild-type (subgroup C) but not by the E1a deletion mutant...

Mutants dl312, dl314, hr1, and hr3 with mutations in region E1A of adenovirus type 5 were defective for the induction of cell cycle abnormalities detectable by flow cytometry, cell DNA replication, thymidine kinase production, and chromosome aberrations and did not synthesize the viral DNA-binding protein (E2A) in rat cells. dl311, a leaky E1A mutant, induced cell cycle effects at high multipli...

Activity of the adeno-associated virus P5 transcriptional control region was found to be induced by adenovirus E1A gene products. A pair of adjacent sequence elements was found to mediate both basal and E1A-induced P5 activity. The first element is a binding site for the major late transcription factor (MLTF), a factor first identified on the basis of its binding to a specific sequence within t...

The efficacy and specificity of treatment are major challenges for cancer gene therapy. Oncolytic virotherapy is an attractive drug delivery platform for cancer gene therapy. In the present study, the dual-specific antitumor oncolytic adenovirus, Ad-Apoptin-hTERT-E1a, was used to infect SW1116 human colorectal carcinoma (CRC) cell lines and CT26 mouse-CRC-cell bearing BALB/c mouse models for te...

Pancreatic beta-cell-type-specific expression of the insulin gene requires both ubiquitous and cell-enriched activators, which are organized within the enhancer region into a network of protein-protein and protein-DNA interactions to promote transcriptional synergy. Protein-protein-mediated communication between DNA-bound activators and the RNA polymerase II transcriptional machinery is inhibit...

Interferons (IFNs) are cytokines that have pleiotropic effects and play important roles in innate and adaptive immunity. IFNs have broad antiviral properties and function by different mechanisms. IFNs fail to inhibit wild-type Adenovirus (Ad) replication in established cancer cell lines. In this study, we analyzed the effects of IFNs on Ad replication in normal human cells. Our data demonstrate...

PURPOSE HER-2/neu oncogene is overexpressed in 10-30% of epithelial ovarian cancers and is associated with a poor prognosis. The E1A gene product of adenovirus type 5 down-regulates HER-2/neu and causes tumor regression in animal models. In the current study, we sought to determine the toxicity and biological activity of E1A-lipid complex in ovarian cancer patients. EXPERIMENTAL DESIGN A Phas...

Ferritin, the major intracellular iron storage protein of eucaryotic cells, is regulated during inflammation and malignancy. We previously reported that transcription of the H subunit of ferritin (ferritin H) is negatively regulated by the adenovirus E1A oncogene in mouse NIH 3T3 fibroblasts (Y. Tsuji, E. Kwak, T. Saika, S. V. Torti, and F. M. Torti, J. Biol. Chem. 268:7270-7275, 1993). To eluc...

Previous detailed mutational analysis has shown that the binding site on adenovirus (Ad) early region 1A (E1A) for TATA-binding protein (TBP) is located toward the N terminus of conserved region 3 (CR3). Here we demonstrate that synthetic peptides of between 15 and 22 amino acids, identical to amino acid sequences of CR3 present in the larger Ad5 E1A (13 S product) and in both the Ad12 E1A (13 ...