Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two p53-related genes, p73 and p51, were recently identified as structural homologues of the p53 tumor suppressor gene, suggesting that the roles of these two genes may be similar to those of p53, including growth suppression and induction of apoptosis. Here we show that introduction of p73 or p51 cDNAs into cultured human cancer cells suppressed colony formation in the presence of G418. We then examined the ability of various isoforms of p73 and p51 to activate transcription of a reporter gene. This assay showed that p73beta and p51A activated transcription through a consensus p53 binding sequence, while p73alpha and p51B isoforms minimally transactivated the p53 reporter gene. To characterize further the biological functions of the p53-related genes, we constructed recombinant adenoviruses containing the p73 and p51 cDNAs. Ad-p73beta and Ad-p51A induced endogenous p21 gene expression more effectively than Ad-p73alpha and Ad-p51B, respectively. To evaluate the mode of cell death induced by p53-related genes, Ad-p73 and Ad-p51 were used to infect human cancer cells. Infection of Ad-p73beta, Ad-p51A or Ad-p51B resulted in DNA fragmentation in a subset of cancer cell lines more efficiently than did infection of Ad-p53. We then examined the combined effect of each p53-related gene and the E1A oncogene in the induction of apoptosis. The E1A oncogene cooperated with p51 as well as p53 to induce apoptosis, while p73 resulted in a weak induction of apoptosis by E1A. Overall, apoptosis induction by p51B and p73alpha isoforms may be due to mechanisms other than transcriptional activation of p53-target genes. Our results suggest that p53-related genes are both similar to and different from p53 in their pathways leading to growth suppression.
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PMID:Adenovirus-mediated transfer of p53-related genes induces apoptosis of human cancer cells. 1076 4

EBV infection has been implicated in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). Viral infection may occur from the early or late stage in IPF development. Whether alveolar epithelial cells, AECs, normally express EBV main receptor, CD21, remains uncertain. Such situations prompted us to exploit an efficient direct infection system to investigate EBV receptor repertoire in primary human AECs. Using human primary type 2 AECs, which have been grown in basal medium supplemented with 10 ng/ml Keratinocyte Growth Factor, and type 1 AECs, supplemented with Epithelial Growth Factor, both AEC lines express CD21 mRNA and protein with a significant increase in type 2 cells. Type 2 AECs have been exposed to TGFbeta1 and IL-4, whose expression is associated with IPF development. CD21 is highly expressed in type 2 AECs following IL-4 exposure. EBV bound to type 2 AECs membrane increases significantly following pre-treatment with IL-4 (p<0.001) and decreasing antagonizing CD21 receptor (p<0.01). 200 microg/ml G418-mediated selection of EBV-Neomycin resistant infected cells selected IL-4 pre-exposed type 2 AECs. Our study of a viral cell line model provides evidence to suggest that CD21-dependent viral entry plays a crucial role in type 2 AECs, indicative of an IL-4 response EBV infection in IPF.
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PMID:IL-4 increases CD21-dependent infection of pulmonary alveolar epithelial type II cells by EBV. 1919 42