The expression of Adenovirus serotype 2 or serotype 5 (Ad2/5) E1A in tumor cells reduces their tumorigenicity in vivo by enhancing the NK cell mediated and T cell mediated anti-tumor immune response, an activity that correlates with the ability of E1A to bind p300. We determined if E1A could be used as a molecular adjuvant to enhance antigen-specific T cell responses to a model tumor antigen, o...

The adenovirus 12S and 13S E1A proteins have been shown to relieve repression mediated by the cellular transcription factor YY1. The 13S E1A protein not only relieves repression but also activates transcription through YY1 binding sites. In this study, using a variety of in vivo and in vitro assays, we demonstrate that both E1A proteins can bind to YY1, although the 13S E1A protein binds more e...

The adenovirus E1A gene encodes five overlapping mRNAs which are processed by alternative RNA splicing from a common pre-mRNA. To characterize cis-acting sequence elements which are of importance for the alternative 5'-splice site selection deletion and substitution mutants within the intron that is common to all E1A mRNAs were constructed. Deletion of the wild-type E1A branch site/polypyrimidi...

DNA tumorviruses like adenoviruses (AdV) or human papillomaviruses (HPV) have adopted various strategies to interfere with antiproliferative transforming growth factor-beta (TGF-beta) signalling. Here we report that the AdV E1A oncoprotein is sufficient to induce Smad7 expression, an inhibitor of TGF-beta signalling. E1A but not HPV oncoproteins activated the Smad7 promoter. A promoter proximal...

The adenovirus E1A 243R oncoprotein is capable of transactivating the expression of the human proliferating cell nuclear antigen (PCNA) promoter. Mutational analysis of the E1A 243R protein suggested that both its p300/CBP- and p107-binding regions are required for optimal induction of the PCNA promoter (C. Kannabiran, G. F. Morris, C. Labrie, and M. B. Mathews, J. Virol. 67:425-437, 1993). We ...

The human adenovirus type 5 (Ad5) early-region 1A (E1A) proteins have been shown to have strong tumor-suppressive activities in human tumor cells and to enhance the sensitivity of a variety of malignant tumors to apoptosis induced by ionizing radiation and chemotherapeutic agents. However, the inherent limitations of E1A gene therapy prevent its application, such as the efficiency of expression...

The adenovirus E1A oncogene induces innate immune rejection of tumors by sensitizing tumor cells to apoptosis in response to injuries, such as those inflicted by macrophage-produced TNF alpha and NO. E1A sensitizes cells to TNF by repressing its activation of NF-kappaB-dependent, antiapoptotic defenses. This suggested the hypothesis that E1A blockade of the NF-kappaB activation response might b...

Epithelial-mesenchymal transformation is now recognised as an important feature of tissue remodelling. The present report concerns the role of adenovirus infection in inducing this transformation in an animal model of chronic obstructive pulmonary disease. Guinea pig primary peripheral lung epithelial cells (PLECs) transfected with adenovirus E1A (E1A-PLECs) were compared to guinea pig normal l...

The RIZ (G3B/MTB-Zf) gene was first isolated based on its ability to bind to the retinoblastoma protein (Rb). An acidic, approximately 100-amino-acid region around the Rb-binding motif of RIZ has structural and antigenic similarity to the conserved sequences of the E1A viral oncogene. We show here that this region interacts specifically with the E1A-binding domain of Rb. This interaction could ...

The leading cause of death in cancer patients is cancer metastasis, for which there is no effective treatment. MicroRNAs (miRNA) have been shown to play a significant role in cancer metastasis through regulation of gene expression. The adenovirus type 5 E1A (E1A) is associated with multiple tumor-suppressing activities including the inhibition of metastasis, and E1A gene therapies have been tes...