The tumor (T) antigens encoded by the human adenovirus early transforming region 1A (E1A) are gene regulatory proteins whose functions can immortalize cells. We have recently described the synthesis in Escherichia coli and the purification of the complete T antigens encoded by the adenovirus type 12 (Ad12) E1A 12S mRNA (235-residue [235R] T antigen) and 13S mRNA (266R T antigen). In this study,...

The adenoviral early region 1A gene (E1A) is a modulator of cellular and viral gene transcription and the primary mediator of cell cycle induction during infection of quiescent cells. It is through these cell cycle effects that E1A can immortalize cells during either abortive infection or stable expression. A side effect of E1A altering cell cycle and host transcriptional activity is that expre...

Glioblastoma multiforme (GBM) is the most aggressive brain tumor, and patients rarely survive for more than 2 years. Gene therapy may offer new treatment options and improve the prognosis for patients with GBM. Adenovirus-mediated gene therapy strategies for brain tumors have been limited by inefficient gene transfer due to low expression of the adenovirus serotype 5 (Ad5) receptor. We have use...

The cdk-inhibitor p21(CIP1/WAF1) inhibits the activities of cyclin-dependent kinases and proliferating cell nuclear antigen, thereby repressing cell-cycle progression and DNA replication. Transforming oncogenes, such as E1A of human adenovirus 5 (Ad5), may interfere with such growth-inhibitory proteins. In this study, we show that in various Ad5E1-transformed cells, p21(CIP1/WAF1) is expressed ...

Adenoviruses are pathological agents inducing mild respiratory and gastrointestinal infections. Under certain circumstances, for example in immunosuppressed patients, they induce severe infections of the liver, heart and lung, sometimes leading to death. Currently, adenoviral infections are treated by palliative care with no curative antiviral therapy yet available. Gene silencing by RNA interf...

Although recombinant human adenovirus (HAV)-based vectors offer several advantages for somatic gene therapy and vaccination over other viral vectors, it would be desirable to develop alternative vectors with prolonged expression and decreased toxicity. Toward this objective, a replication-defective bovine adenovirus type 3 (BAV-3) was developed as an expression vector. Bovine cell lines designa...

We have examined the mechanism for the host cell-dependent repression of enhancer activity by the adenovirus early region 1A (E1A) proteins. The enhancer used in this study, from the human BK virus P2, functions efficiently in cis to activate expression from the adenovirus major late promoter in the human kidney cell line, 293, and in a monkey kidney cell line, MK2. In addition, enhancer activi...

The CR3 activation domain of the human adenovirus E1A protein stimulates transcription by forming protein-protein interactions with DNA sequence-specific binding factors and components of the TFIID complex. Here, we demonstrate that CR3 can complex with the extreme C-terminal 105 amino acids of the human TATA box binding-factor-associated protein, hTAF(II)135. Furthermore, the C-terminal region...

The early region 1A of adenoviruses encodes two multifunctional proteins that have varied effects on viral and host cell transcription. Expression of adenovirus 5 E1A in the mouse myogenic cell line 23A2 inhibits the differentiation of the cells and represses the expression of reporter genes controlled by several muscle-specific regulatory elements. In addition, differentiation-defective 23A2 E...

In highly oncogenic adenovirus (Ad) 12-transformed cells, major histocompatibility complex (MHC) class I gene expression is down-regulated by the products of the viral E1A oncogene at the level of initiation of transcription. However, class I gene expression is unaltered or elevated in non-oncogenic Ad2- or Ad5-transformed cells. These changes in class I expression may permit Ad12-transformed c...