Structure of two spliced mRNAs from the transforming region of human subgroup C adenoviruses

Perricaudet, Michel; Akusjärvi, Göran; Virtanen, Anders; Pettersson, Ulf

doi:10.1038/281694a0

Cited by 366 publications

(223 citation statements)

References 17 publications

Supporting

Mentioning

221

Contrasting

Order By: Relevance

“…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).…”

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

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

show abstract

“…Two different splice products, the 12S and 13S mRNAs, are formed from the ElA region early in infection (4,12,33,48). These products are predicted to encode proteins 243 and 289 amino acids long, respectively, distinguished only by the presence of the 46 amino acids at positions 140 through 185 which are unique to the 13S product.…”

mentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…The single point mutation in hr5 ElA produces a different amino acid substitution in the 289R and 243R proteins (16). These simultaneous missense mutations occur because the altered nucleotide serves as the middle base of a split codon for each mRNA that is formed as a result of differential splicing (41). In the 289R protein of hr5, asparagine replaces serine as the last amino acid in the unique region (residue 185), whereas in the 243R protein, aspartic acid replaces glycine as the last amino acid before the unique region (residue 139) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Upon adenovirus type 5 (AdS) infection of HeLa cells, two overlapping ElA transcripts of 12S and 13S are the first viral mRNAs synthesized (2,28). These transcripts are 5' and 3' co-terminal and share the same acceptor splice site but utilize different donor splice sites (3,41,49 (39,42). This suggests that the 46R region that is unique to the larger of the ElA proteins contains information that is essential for transactivation of early promoters.…”

mentioning

confidence: 99%

An adenovirus type 5 E1A protein with a single amino acid substitution blocks wild-type E1A transactivation.

Glenn¹,

Ricciardi²

1987

Mol. Cell. Biol.

View full text Add to dashboard Cite

The ElA gene of adenovirus type 5 encodes a 289-amino-acid (289R) protein that transactivates early adenovirus promoters. We showed that the 289R protein of the EIA missense mutant gene hr5 is novel in that it inhibits the wild-type (wt) ElA protein from stimulating transcription from each of the early viral promoters E2, E3, and E4. Since both the hr5 and wt genes produced similar levels of ElA proteins, the ability of hr5 ElA to block transactivation was attributed to the replacement of serine by asparagine as position 185. We confirmed that this single amino acid substitution was responsible for blocking transactivation by showing equal inhibition with an hr5-wt hybrid ElA gene containing this missense mutation as the only alteration. The smaller 243R ElA protein of hr5 was not necessary for inhibition. Transcriptional activity from each early promoter was inhibited by at least 50% when the hr5 and wt ElA genes were present in equimolar amounts; complete inhibition occurred with a fivefold molar excess of the hr5 gene. Two other ElA missense mutant genes (hr3 and hr4) with amino acid substitutions in close proximity to that of hr5 failed to block wt ElA-induced transcription when similarly tested. Also, the hr5 ElA gene failed to impede the pseudorabies immediate early gene from transactivating the adenovirus E3 promoter, demonstrating that hr5 ElA inhibits wt ElA activation at the transcriptional, rather than the posttranscriptional, level. Although several possibilities were considered to account for this inhibition, the most likely is that the nonfunctional hr5 ElA protein competes with the wt 289R protein for a cellular transcription factor required for transactivation.

show abstract

Structure of two spliced mRNAs from the transforming region of human subgroup C adenoviruses

Cited by 366 publications

References 17 publications

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

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

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

An adenovirus type 5 E1A protein with a single amino acid substitution blocks wild-type E1A transactivation.

Contact Info

Product

Resources

About