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Biomedical subjects

C Egan

Publications and source records attributed to C Egan.

26 records · Page 2Linked to original sources
PubMed1990

Retinoblastoma growth suppressor and a 300-kDa protein appear to regulate cellular DNA synthesis.

Previous work has suggested that oncogenic transformation by the E1A gene products of adenovirus type 5 may be mediated through interactions with at least two cellular proteins, the 105-kDa product of the retinoblastoma growth suppressor gene (p105-Rb) and a 300-kDa protein (p300). By using viral mutants, we now show that the induction of cellular DNA synthesis in quiescent cells by E1A differs from transformation in that E1A products induce synthesis if they are able to bind to either p105-Rb or p300, and only mutant products that bind to neither are extremely defective. These results suggest that p105-Rb and p300 (or cellular proteins with similar E1A-binding properties) provide parallel means by which DNA synthesis can be regulated.

Adenovirus Early Proteins↗
PubMed1989

Skeletal muscle glutamine transport, intramuscular glutamine concentration, and muscle-protein turnover.

This article reviews work we have carried out to investigate (1) the transport mechanisms responsible for the high distribution ratio of free glutamine commonly observed in skeletal muscle; (2) the fall in the distribution ratio that accompanies starvation, injury and chronic disease, whether directly involving muscle or not; and (3) the effect of modulation of intracellular free-glutamine concentration on protein synthesis and breakdown in skeletal muscle. We suggest that the results are consistent with the controlling role of the muscle membrane glutamine-sodium cotransporter in the regulation of the intracellular glutamine pool, the existence of pathophysiological mechanisms for the modulation of intramuscular glutamine and anabolic effects of glutamine in promoting protein synthesis, with a smaller effect in reducing protein breakdown. The mechanisms by which glutamine affects skeletal muscle protein turnover, and thus muscle protein balance, and the extent of the net flow of amino acids between the periphery and the viscera are unknown as yet, but the results suggest that modulation of transporter activity may offer the possibility of therapeutic intervention to reduce muscle wasting associated with injury and disease.

Animals↗
PubMed1989

Binding of the Rb1 protein to E1A products is required for adenovirus transformation.

Several cellular proteins, including polypeptides of 300, 107 and 105kDa, associate with the products of the E1A gene of adenovirus type 5. Here we show that the 105kDa species is the product of the recessive oncogene Rb1 which is absent or altered in retinoblastomas and other human cancers. About 75% of the total Rb1 protein in infected human KB cells was found to be complexed with E1A products and these data support the hypothesis that E1A-mediated transformation results from the elimination of functional Rb1 protein within the cell. However, while the interaction of E1A products with this cellular protein is necessary, transformation appears also to require binding of the 300 and 107kDa polypeptides. We also found that both the Rb1 protein and the 107kDa E1A-binding species were undetectable in a retinoblastoma cell line lacking both alleles of the Rb1 gene. These data suggest that the absence of both the 107kDa and 105kDa/Rb1 proteins may be involved in the development of the oncogenic phenotype of retinoblastoma cells.

Adenovirus Early Proteins↗
PubMed1988

Mapping of cellular protein-binding sites on the products of early-region 1A of human adenovirus type 5.

The binding sites for the 300-, 107-, and 105-kilodalton cellular proteins which associate with human adenovirus type 5 E1A products were studied with E1A deletion mutants. All appeared to bind to the amino-terminal half of E1A products in regions necessary for oncogenic transformation. These results suggest that these cellular species may be important for the biological activity of E1A products.

Adenovirus Early Proteins↗
PubMed1987

Binding of cellular polypeptides to human adenovirus type 5 E1A proteins produced in Escherichia coli.

Cellular proteins of 300, 107, 105, 68 and 65 kDa have previously been shown to associate specifically with the early region 1A (E1A) proteins of human adenovirus type 5. In the present study we report that, to varying degrees, these proteins also were capable of binding to E1A products produced in Escherichia coli from plasmids carrying cDNAs corresponding to the 1.1- and 0.9-kb E1A mRNAs. When these purified E1A proteins were mixed in solution with extracts from mock-infected human cells, the 68- and 65-kDa species bound very efficiently to the 1.1-kb mRNA product and somewhat less so with that of the 0.9-kb mRNA. The 107-, 105-, and 300-kDa species bound poorly, if at all, to both E1A products. Using the E1A 1.1-kb mRNA product which had been covalently attached to Sepharose beads, the 68-, 65-, and 300-kDa species bound efficiently, and binding of protein which migrated in SDS gels in the region of the 107- and 105-kDa species was also observed. In addition to these proteins, several other cellular polypeptides of 30, 33, 75, 95, 150, 180, and greater than 300 kDa were shown to bind to E1A-Sepharose and thus may also be E1A-binding proteins. The present data confirm the specificity of the previously identified cellular proteins for E1A products and show that binding of the 300-, 65-, and 68-kDa species does not require the presence of any other viral polypeptide. In contrast, the inefficient binding of the 107- and 105-kDa species to Escherichia coli-expressed E1A protein may suggest that these interactions require either eukaryotic-specific post-translational modifications of the E1A protein, or the presence of additional Ad5 gene products.

Adenovirus Early Proteins↗
PubMed1986

Different patterns of protein turnover in skeletal and gastrointestinal smooth muscle and the production of N tau-methylhistidine during fasting in the rat.

During four days of fasting in rats skeletal muscle protein synthesis fell progressively, whereas skeletal muscle protein breakdown was unchanged until the third and fourth days when it rose dramatically. In contrast, the synthetic rate of smooth muscle protein was unchanged during three days of fasting despite a loss of protein content, indicating an abrupt rise in protein breakdown in this tissue on the first day of fasting which was sustained thereafter. Urinary excretion of N tau-methylhistidine was significantly increased throughout fasting. The concentration of free N tau-methylhistidine in plasma and in muscle tissue was elevated throughout the period of fasting. This elevation was not caused by reduced renal clearance, but appears to have been mainly the result of increased breakdown of N tau-methylhistidine-containing proteins in tissues other than skeletal muscle.

Animals↗