Dissection of overlapping functions within the adenovirus type 5 E1A gene.

Winberg, Gösta; Shenk, Thomas

doi:10.1002/j.1460-2075.1984.tb02066.x

Cited by 144 publications

(121 citation statements)

References 34 publications

(26 reference statements)

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“…In most experiments, there was a clear increase of E2 RNA in a d11500 infection compared with that in a dl312 infection. This is consistent with other studies that demonstrated an induction of viral transcription by the 12S ElA product (8,24,52). We conclude that the 12S ElA gene product does possess transcription-inducing activity but that the efficiency of this activity depends on the target gene.…”

Section: Simon Et Al In Preparation)supporting

confidence: 93%

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

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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.

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Section: Simon Et Al In Preparation)supporting

confidence: 93%

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

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“…Some studies (34,51,70) indicate that the 12S product is able to trans activate adenovirus early region genes as efficiently as the 13S product. We found that 12S-infected primary BRK cells eventually expressed the adenovirus E2A DBP and the cellular TS gene product, but there was greatly accelerated expression of these genes in 13S virus-infected primary BRK cells.…”

Section: Discussionmentioning

confidence: 99%

Different functional domains of the adenovirus E1A gene are involved in regulation of host cell cycle products.

Zerler¹,

Roberts²,

Mathews³

et al. 1987

Mol. Cell. Biol.

176

141

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We have analyzed the ceH cycle effects that different domains of the adenovirus EIA proteins have on quiescent primary BRK cells. Studies with deletion mutants that in combination removed all but the N-terminal 85 amino acids common to both the 12S and 13S proteins suggest that this region may be sufficient for the induction of synthesis of proliferating cell nuclear antigen and the stimulation of DNA synthesis. A second domain also common to the N-terminal exon of the 12S and 13S proteins was required for the induction of mitosis and stimulation of proliferation of primary BRK cells. A virus containing a mutation in this region was still able to stimulate DNA synthesis efficiently. A third domain, unique to the 13S protein, was required for the accelerated activation of the cellular thymidylate synthase gene in a manner similar to the 13S-dependent stimulation of adenovirus early region genes.

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“…In part, this is likely due to a variability of results. In particular, some experiments have indicated that the 12S product does not trans-activate at all (Lillie et al 1986(Lillie et al , 1987Moran et al 1986a, b), whereas others have described activity that is reduced compared to that of the 13S product and possibly was only significant for certain cellular targets (Winberg and Shenk 1984;Simon et al 1987;Zerler et al 1987). Other studies demonstrated that the 12S E1A activation was nearly as strong as the 13S activation and that early viral genes, including the E2 gene, could be the targets of activation (Leff et al 1984;Ferguson et al 1985).…”

Section: A Biochemical Mechanism For Transcription Activation Mediatementioning

confidence: 99%

Domains of the adenovirus E1A protein required for oncogenic activity are also required for dissociation of E2F transcription factor complexes.

Bagchi²,

et al. 1991

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Recent experiments have shown that the cellular E2F transcription factor is found in complexes with cellular proteins and that one such complex contains the cyclin-A protein. Isolation of a cellular activity, which we term E2F-BF, can reconstitute the E2F-cyclin-A complex and has permitted a more detailed analysis of the mechanism of E1A dissociation. Through the analysis of a series of EIA mutants, we find that sequences in conserved region 1 (CR1) and conserved region 2 (CR2) are important for dissociation of the E2F complex, whereas amino-terminal sequences are not required. In contrast to the requirements for dissociation, only the CR1 sequences are required to block formation of the complex if E1A is added when the components are combined. We have also identified an activity, termed E2F-I, that inhibits E2F binding to DNA, again apparently through the formation of a complex with E2F. This inhibitory activity is also blocked by E1A, dependent on the same elements of the E1A protein that disrupt the interaction with E2F-BF. Because the E1A sequences that are important for releasing E2F from these interactions are also sequences necessary for oncogenesis, we suggest that this activity may be a critical component of the transforming activity of E1A.

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Dissection of overlapping functions within the adenovirus type 5 E1A gene.

Cited by 144 publications

References 34 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.

Different functional domains of the adenovirus E1A gene are involved in regulation of host cell cycle products.

Domains of the adenovirus E1A protein required for oncogenic activity are also required for dissociation of E2F transcription factor complexes.

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