| pubmed-article:12915548 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12915548 | lifeskim:mentions | umls-concept:C0007634 | lld:lifeskim |
| pubmed-article:12915548 | lifeskim:mentions | umls-concept:C1704256 | lld:lifeskim |
| pubmed-article:12915548 | lifeskim:mentions | umls-concept:C0597357 | lld:lifeskim |
| pubmed-article:12915548 | lifeskim:mentions | umls-concept:C1709313 | lld:lifeskim |
| pubmed-article:12915548 | pubmed:issue | 17 | lld:pubmed |
| pubmed-article:12915548 | pubmed:dateCreated | 2003-8-13 | lld:pubmed |
| pubmed-article:12915548 | pubmed:abstractText | Transforming growth factor beta1 (TGF-beta1) signaling is compromised in many tumors, thereby allowing the tumor to escape the growth-inhibitory and proapoptotic activities of the cytokine. Human adenoviruses interfere with a number of cellular pathways involved in cell cycle regulation and apoptosis, initially placing the cell in a "tumor-like" state by forcing quiescent cells into the cell cycle and also inhibiting apoptosis. We report that adenovirus-infected cells resemble tumor cells in that TGF-beta1 signaling is inhibited. The levels of TGF-beta1 receptor II (TbetaRII) in adenovirus-infected cells were decreased, and this decrease was mapped, by using virus mutants, to the E1A gene and to amino acids 2 to 36 and the C-terminal binding protein binding site in the E1A protein. The decrease in the TbetaRII protein was accompanied by a decrease in TbetaRII mRNA. The decrease in TbetaRII protein levels in adenovirus-infected cells was greater than the decrease in TbetaRII mRNA, suggesting that downregulation of the TbetaRII protein may occur through more than one mechanism. Surprisingly in this context, the half-lives of the TbetaRII protein in infected and uninfected cells were similar. TGF-beta1 signaling was compromised in cells infected with wild-type adenovirus, as measured with 3TP-lux, a TGF-beta-sensitive reporter plasmid expressing luciferase. Adenovirus mutants deficient in TbetaRII downregulation did not inhibit TGF-beta1 signaling. TGF-beta1 pretreatment reduced the relative abundance of adenovirus structural proteins in infected cells, an effect that was potentiated when cells were infected with mutants incapable of modulating the TGF-beta signaling pathway. These results raise the possibility that inhibition of TGF-beta signaling by E1A is a means by which adenovirus counters the antiviral defenses of the host. | lld:pubmed |
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| pubmed-article:12915548 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12915548 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12915548 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12915548 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:12915548 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12915548 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:12915548 | pubmed:issn | 0022-538X | lld:pubmed |
| pubmed-article:12915548 | pubmed:author | pubmed-author:WoldWilliam... | lld:pubmed |
| pubmed-article:12915548 | pubmed:author | pubmed-author:TarakanovaVer... | lld:pubmed |
| pubmed-article:12915548 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12915548 | pubmed:volume | 77 | lld:pubmed |
| pubmed-article:12915548 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12915548 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12915548 | pubmed:pagination | 9324-36 | lld:pubmed |
| pubmed-article:12915548 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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| pubmed-article:12915548 | pubmed:year | 2003 | lld:pubmed |
