An adenovirus E1a protein region required for transformation and transcriptional repression

Lillie, James W.; Green, Maurice; Green, Michael R.

doi:10.1016/0092-8674(86)90704-x

Cited by 336 publications

(279 citation statements)

References 42 publications

Supporting

Mentioning

264

Contrasting

Order By: Relevance

“…More to the point are various studies that show that the 12S product can effect immortalization and at least partial transformation in the absence of the 13S product. Since the 13S product is necessary for normal viral transcription activation, it has been suggested that the ElA transcription-inducing activity is not required for transformation (25,31). However, the results presented in this report must alter these arguments since it was found that the hsp7O gene can be induced by the 12S ElA gene product.…”

Section: Simon Et Al In Preparation)mentioning

confidence: 65%

“…It might be anticipated that the transcriptional regulatory activity of ElA with respect to cellular genes might be part of this process. For instance, a role for ElA-mediated transcriptional repression in adenovirus transformation has been suggested (25,33). The ElA proteins can repress the activity of the simian virus 40, polyomavirus, or Ad2 ElA enhancers in transfection experiments (3,50) and the transcription of endogenous immunoglobulin genes (11).…”

Section: Simon Et Al In Preparation)mentioning

confidence: 99%

“…The ElA proteins can repress the activity of the simian virus 40, polyomavirus, or Ad2 ElA enhancers in transfection experiments (3,50) and the transcription of endogenous immunoglobulin genes (11). Several transformation-defective ElA mutants have been identified that are positive for induction of the E2, E3, and E4 mRNAs, as well as the human P-globin gene cloned into the adenovirus genome (25,33). However, these transformation-defective mutants failed to repress a gene linked to the simian virus 40 enhancer, as well as endogenous cellular genes.…”

Section: Simon Et Al In Preparation)mentioning

confidence: 99%

See 2 more Smart Citations

Selective induction of human heat shock gene transcription by the adenovirus E1A gene products, including the 12S E1A product.

Simon¹,

Kitchener²,

Kao³

et al. 1987

Mol. Cell. Biol.

111

View full text Add to dashboard Cite

We have previously shown that the human 70-kilodalton heat shock protein gene (hsp7O) is induced by the adenovirus ElA gene product and during the S-G2 phase of the cell cycle. In this study, we investigated the effect of ElA on the expression of other human hsp genes. A gene encoding one form of the hsp89 protein (hsp89a) was activated during an adenovirus infection with kinetics similar to those of activation of hsp7O. The induction required a functional ElA gene. However, the hsp89 transcript was not cell cycle regulated. Genes encoding another form of hsp89 and the hsp27 protein were not induced by ElA or during the cell cycle. Further examination of hsp7O expression revealed a greater complexity than previously seen. Si nuclease analysis using an hsp70 cDNA as well as a distinct hsp7O genomic clone demonstrated three related hsp70 transcripts; two were induced by ElA, and one was not. Both of the ElA-inducible genes were regulated during the cell cycle. All three were induced by heat shock. These results suggest common aspects of control among certain members of this family of cellular genes distinct from heat shock control. Finally, using viruses that express the individual ElA proteins, we found that the hsp70 gene is induced by the 12S and the 13S ElA products. The efficiency of induction by the 12S product was somewhat less than that by the 13S product but only by a factor of less than 2. This is in contrast to the induction of early viral genes, for which the 13S product is considerably more efficient than the 12S product.

show abstract

Section: Simon Et Al In Preparation)mentioning

confidence: 65%

Section: Simon Et Al In Preparation)mentioning

confidence: 99%

Section: Simon Et Al In Preparation)mentioning

confidence: 99%

See 1 more Smart Citation

Selective induction of human heat shock gene transcription by the adenovirus E1A gene products, including the 12S E1A product.

Simon¹,

Kitchener²,

Kao³

et al. 1987

Mol. Cell. Biol.

111

View full text Add to dashboard Cite

show abstract

“…At early times of infection, the E1A gene produces two transcripts, 12S and 13S in size, which encode products of 243 and 289 amino acids, respectively (Berk and Sharp 1978;Chow et al 1979;Perricaudet et al 1979;Kitchingman and Westphal 1980). Both products display regulatory activity; the product of 289 amino acids can trans-activate and repress gene transcription (Borrelli et al 1984;Velcich and Ziff 1985), whereas the protein of 243 amino acids, although it represses very efficiently (Borrelli et al 1984;Velcich and Ziff 1985), is generally found to be deficient in trans-activation (Carlock and Jones 1981;Montell et al 1982;Svensson and Akusjarvi 1984;Winberg and Shenk 1984;Lillie et al 1986;Moran et al 1986;Wu et al 1986a). Furthermore, extensive mutational analysis of the E1A gene has identified domains that are required for repression but not for trans-activation (Lillie et al 1986;Moran et al 1986;Schneider et al 1987).…”

mentioning

confidence: 99%

Identification of factors that interact with the E1A-inducible adenovirus E3 promoter.

Hurst

Jones²

1987

Genes Dev.

185

195

View full text Add to dashboard Cite

We have investigated the E1A-inducible E3 promoter of adenovirus type 5 with respect to its ability to bind specific nuclear proteins. Four distinct nucleoprotein-binding sites were detected, located between positions -7 to -33, -44 to -68, -81 to -103, and -154 to -183, relative to the E3 cap site. These sites contain sequences previously shown to be functionally important for efficient E3 transcription. No major qualitative or quantitative differences were found in the binding pattern between nucleoprotein extracts prepared from uninfected or adenovirus-infected HeLa cells. Competition experiments suggest that the factors binding to the -154 to -183 and -81 to -103 sites are the previously identified nucleoproteins, NFI and AP1, respectively. The factor binding to the -44 to -68 site, which we term ATF, also interacts with other E1A-inducible promoters and is very similar and probably identical to the factor that binds to the cAMP-responsive element of somatostatin. We have purified this factor, which is a protein of 43 kD in size.

show abstract

“…The E1A CR2 domain is known to bind with the RB family of proteins, leading to immortalization of the primary culture cells and in cooperation with ras or E1B oncogenes, E1A can lead to transformation (Whyte et al, 1989;Corbeil and Branton, 1994). Deletion of the CR2 domain or even a site mutation to knock out the RB-binding site on E1A is su cient to abolish the immortalization function of E1A (Lillie et al, 1986;Moran et al, 1986;Zerler et al, , 1987Schneider et al, 1987;Kuppuswamy and Chinnadurai, 1987;Smith and Zi , 1988;Jelsma et al, 1989;Whyte et al, 1989). Thus, the deletion of the CR2 and CR3 domains in the mini-E1A would abolish the potential risk of immortalization and consequent transformation caused by wild type E1A.…”

Section: Discussionmentioning

confidence: 99%

Mapping of adenovirus 5 E1A domains responsible for suppression of neu-mediated transformation via transcriptional repression of neu

Chen

Chinnadurai

et al. 1997

Oncogene

View full text Add to dashboard Cite

Overexpression of neu (also known as c-erbB-2 or HER-2) commonly occurs in human cancer and is also known to enchance tumor metastasis and chemoresistance. Our earlier reports showed that the adenovirus 5 E1A can suppresss the neu-mediated transformation by repression of neu. Thus, E1A has the potential to be used as a therapeutic agent against the neu-overexpressing human cancers. However, a serious concern to this approach is that E1A is also capable of immortalizing primary culture cells and can co-operate with ras or E1B oncogenes to transform them. The E1A CR2 domain (amino acid residues 120 to 140) necessary for binding to RB is believed to be required for this oncogenic function. Here, we report that deletion of CR2 region did not a ect E1A's capability to repress neu. Interestingly, deletion of the amino acid residues 4 to 25 or 40 to 80 completely disrupted E1A-mediated neu repression. By deleting the amino acid residues from 81 to 185, we have successfully generated a mini-E1A mutant that was su cient to inhibit neu promoter activity and suppress neu-mediated transformation. The mini-E1A mutant does not contain the CR2 domain that is crucial for RB binding and immortalization, and hence, may serve as a more selective tumor suppressor, and a safer therapeutic agent. It may also be a useful tool to further investigate the molecular mechanism(s) of neu overexpression and E1A-mediated transcriptional repression in cancer cells.

show abstract

An adenovirus E1a protein region required for transformation and transcriptional repression

Cited by 336 publications

References 42 publications

Selective induction of human heat shock gene transcription by the adenovirus E1A gene products, including the 12S E1A product.

Selective induction of human heat shock gene transcription by the adenovirus E1A gene products, including the 12S E1A product.

Identification of factors that interact with the E1A-inducible adenovirus E3 promoter.

Mapping of adenovirus 5 E1A domains responsible for suppression of neu-mediated transformation via transcriptional repression of neu

Contact Info

Product

Resources

About