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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1993-7-9
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pubmed:abstractText |
Adenovirus-(Ad)- E1A proteins carry two conserved domains (CR1 and CR2) required for transformation of primary rodent cells and essential for association with cellular proteins, including p105RB, p58cyclin A and p33cdk2. We show that in normal rat kidney 49F (NRK) cell lines expressing various mutant Ad5-E1A genes, CR2-, but not CR-1-, deletion mutants induce a typical transformed phenotype as characterized by morphology, absence of density arrest and loss of serum requirement. This indicates that induction of these transformed properties is a function of CR1. The fact that E1A proteins with deletions in CR2 show a greatly reduced association with RB, cyclin A and p33cdk2 suggests that these associations are dispensable for E1A-mediated transformation of NRK cells. Induction of the transformed properties is accompanied by a CR1-dependent increase in Proliferating Cell Nuclear Antigen and cyclin A gene expression. Elevated mRNA and protein levels of cyclin A were also found in Ad12-E1-transformed NRK cells but not in ras-transformed NRK cells. On the other hand, cyclin D expression is decreased in a CR1-dependent manner. Although Ad5-E1A proteins are sufficient to transform NRK cells, further deregulation of growth is obtained when Ad5-E1B proteins are co-expressed. One of the Ad5-E1B effects is the sequestration of the p53 protein into a cytoplasmic body containing the p53/Ad5-E1B-55 kD complex. Interestingly, in NRK cell lines expressing Ad5-E1B-55 kD, cyclin A could be detected not only in the nucleus but also in the cytoplasmic bodies. These results indicate that the deregulation of cell cycle control by the Adenovirus-E1 region may be due to a CR1-dependent alteration of the expression of cyclins A and D.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0950-9232
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1765-73
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8510923-Adenovirus E1A Proteins,
pubmed-meshheading:8510923-Amino Acid Sequence,
pubmed-meshheading:8510923-Animals,
pubmed-meshheading:8510923-Cell Line, Transformed,
pubmed-meshheading:8510923-Cell Transformation, Neoplastic,
pubmed-meshheading:8510923-Cyclins,
pubmed-meshheading:8510923-Molecular Sequence Data,
pubmed-meshheading:8510923-Mutation,
pubmed-meshheading:8510923-Rats,
pubmed-meshheading:8510923-Structure-Activity Relationship
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pubmed:year |
1993
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pubmed:articleTitle |
Increased cyclin A and decreased cyclin D levels in adenovirus 5 E1A-transformed rodent cell lines.
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pubmed:affiliation |
Inserm U55, Centre de Recherches Paris Saint-Antoine, France.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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