The role of adenovirus early region 1A in the regulation of early regions 2A and 1B expression

Rossini, Mara

doi:10.1016/0042-6822(83)90532-9

Cited by 39 publications

(27 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…E1A is the first gene expressed from the adenovirus genome and controls the expression of other virus genes. 25,26 The enhancement of its selective expression in tumor cells may result in an increase of oncolytic potency. In this regard, ICOVIR-7 was able to restore E1A levels similar to AdwtRGD on all tested cancer cell lines, as analyzed by western blot (Figure 4b).…”

Section: Icovir-7 Replication Is Restricted In Normal Cellsmentioning

confidence: 99%

A modified E2F-1 promoter improves the efficacy to toxicity ratio of oncolytic adenoviruses

et al. 2009

View full text Add to dashboard Cite

The E2F-1 promoter has been used to confer tumorselective E1A expression in oncolytic adenoviruses. Tumor specificity is mainly conferred by a unique structure of E2F-responsive sites organized in palindromes. Binding of the E2F-pRb complex to these palindromes results in repression of transcription in normal cells. Owing to deregulation of the Rb/p16 pathway in tumor cells, binding of free E2F activates transcription and initiates an autoactivation loop involving E1A and E4-6/7. ICOVIR-7 is a new oncolytic adenovirus designed to increase the E2F dependency of E1A gene expression. It incorporates additional palindromes of E2F-responsive sites in an insulated E2F-1 promoter controlling E1A-D24. The E2F palindromes inhibited replication in normal cells, resulting in a low systemic toxicity at high doses in immunocompetent mice. The D24 deletion avoids a loop of E2F-mediated selfactivation in nontumor cells. Importantly, the additional E2F-binding hairpins boost the positive feedback loop on the basis of E1A-mediated transcriptional regulation of E4-6/7 turned on in cancer cells and increased antitumoral potency as shown in murine subcutaneous xenograft models treated by intravenous injection. These results suggest that the unique genetic combination featured in ICOVIR-7 may be promising for treating disseminated neoplasias.

show abstract

Section: Icovir-7 Replication Is Restricted In Normal Cellsmentioning

confidence: 99%

A modified E2F-1 promoter improves the efficacy to toxicity ratio of oncolytic adenoviruses

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Rossini (36) has shown that Ela products repress transcription from the Ad2 E2a promoter at 72 m.u. while stimulating transcription from the E2a early promoter at 75 m.u.…”

Section: Discussionmentioning

confidence: 99%

Vector expression of adenovirus type 5 E1a proteins: evidence for E1a autoregulation.

Smith¹,

Kegler²,

Ziff³

1985

Mol. Cell. Biol.

View full text Add to dashboard Cite

We transiently expressed adenovirus type C Ela proteins in wild-type or mutant form from plasmid vectors which have different combinations of Ela and simian virus 40 enhancer elements and which contain the DNA replication origin of SV40 and can replicate in COS 7 cells. We measured the levels of Ela mRNA encoded by the vectors and the transition regulation properties of the protein products. Three vectors encoded equivalent levels of Ela The protein products of the adenovirus Ela transcription unit activate, in trans, viral and cellular promoters and also have a role in adenoviral immortalization and transformation of primary cells (2,8,17,20,21,29,30,37,39,44,46,51). In a productive infection, the Ela transcription unit, situated between 1.5 and 4.5 map units (m.u.) on the viral genome, is expressed from the onset of infection (31) through the action of multiple enhancer elements which activate transcription of the gene by a cis mechanism (14,15,18,33). Ela then stimulates transcription from all other viral promoters, including the four promoters of the classical early regions, Elb, E2, E3, and E4; the Ela promoter itself (2); and the major late promoter, which dominates viral transcription at late times but is also active with reduced efficiency during the early period (2,20,30,35 (4,7,23,28,29,45,51

show abstract

“…is active. Early transcription of region E2A is stimulated by gene products encoded by region E 1 (Berk et al, 1979;Shenk et al, 1979;Nevins, 1981;Montell et al, 1982;Rossini, 1983;Imperiale & Nevins, 1984). For our studies of integration of early region E2A in the genome of human cells we have constructed plasmids containing the Ad5 DBP gene as well as the HSV tk gene.…”

Section: Introductionmentioning

confidence: 99%

Transformation of Human 143 tk- Cells with Plasmids Containing the Gene Encoding the Adenovirus DNA-binding Protein

Laanen

Zelle

Lenstra

et al. 1985

Journal of General Virology

View full text Add to dashboard Cite

SUMMARYHuman cell lines that contain and express the gene encoding the adenovirus type 5 DNA-binding protein (Ad5 DBP) are very useful for the isolation of adenovirus mutants with an altered DBP. In order to obtain these cells, human 143 tk-cells were transfected, using the calcium phosphate technique, with plasmids containing the Ad5 DBP gene and the herpes simplex virus thymidine kinase (HSV tk) gene as a selectable marker. Characterization of several tk ÷ transformants revealed that these cells did contain the HSV tk gene, but in none of these cells could Ad5 DBP DNA sequences be detected. However, when 143 tk-cells were co-transfected with a plasmid containing the Ad5 DBP gene and another plasmid carrying early region El, integration of the Ad5 DBP gene in chromosomal DNA could be detected. Integration of Ad5 DNA sequences was also observed when transfection was performed with plasmids containing the Ad5 DBP gene and the long terminal repeat of Moloney murine leukaemia virus. By employing a radioimmunoassay it could be shown that DBPrelated proteins were synthesized in two of the cell lines containing'the Ad5 DBP gene. Since both cell lines support the growth of the temperature-sensitive viral DBP mutant, H5ts125, at the non-permissive temperature, the DBP-related proteins expressed in these cells must be functional.

show abstract

The role of adenovirus early region 1A in the regulation of early regions 2A and 1B expression

Cited by 39 publications

References 25 publications

A modified E2F-1 promoter improves the efficacy to toxicity ratio of oncolytic adenoviruses

A modified E2F-1 promoter improves the efficacy to toxicity ratio of oncolytic adenoviruses

Vector expression of adenovirus type 5 E1a proteins: evidence for E1a autoregulation.

Transformation of Human 143 tk- Cells with Plasmids Containing the Gene Encoding the Adenovirus DNA-binding Protein

Contact Info

Product

Resources

About