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)

Human papillomavirus type 6 (HPV-6) is the etiologic agent of genital warts and recurrent respiratory papillomatosis. We are investigating the mechanism by which this virus stimulates cell proliferation during infection. In this paper, we report that the E5a gene of HPV-6c, an independent isolate of HPV-11, is capable of transforming NIH 3T3 cells. The E5a open reading frame (ORF) was expressed under the control of the mouse metallothionein promoter in the expression vector pMt.neo.1, which also contains the gene for G418 resistance. Transfected cells were selected for G418 resistance and analyzed for a transformed phenotype. The transformed NIH 3T3 cells overgrew a confluent monolayer, had an accelerated generation time, and were anchorage independent. In contrast, E5a did not induce foci in C127 cells, but C127 cells expressing E5a did form small colonies in suspension. The presence of the 12-kilodalton E5a gene product in the transformed NIH 3T3 cells was shown by immunoprecipitation and was localized predominantly to nuclei by an immunoperoxidase assay. A mutation in the E5a ORF was engineered to terminate translation. This mutant was defective for transformation, demonstrating that translation of the E5a ORF is required for biological activity. This is the first demonstration of a transforming oncogene in HPV-6, and the differential activity of E5a in these two cell lines should facilitate future investigations on the mechanism of transformation.
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PMID:Transforming activity of E5a protein of human papillomavirus type 6 in NIH 3T3 and C127 cells. 216 39

Human papillomavirus (HPV) DNA is found in nature mostly in an episomal form. However, in permanent cell lines established from cervical carcinomas in which HPV sequences are present, they are usually integrated in the host genome. In vitro studies of HPV have been hampered because of the difficulty of stably maintaining HPV sequences in transfected cells. We have cloned the entire HPV6 genome into three vectors: pML2, a derivative of pBR322 lacking the "poison sequences"; p142-6, a plasmid containing the complete bovine papillomavirus type 1 (BPV-1) genome which usually remains extrachromosomal in transfected mouse cells; and p302-3, a plasmid containing the bacterial gene conferring resistance to neomycin. Each of the three constructs has been transfected onto C127 mouse cells. In the case of the recombinant molecules cloned into pML2 and into p42-6, the transfection had been done together with the p302-3 plasmid. G418 resistant colonies were selected and analyzed for their DNA content. In all cases (5/5) the transfected molecules were present and integrated in the cellular genome. No free episomal DNA was detected, even in the cells transfected with the BPV-1 containing plasmid. One junction with the flanking cellular sequences is located in the late open reading frames region of the HPV6 genome and there is a disruption of the early region, as has been described for the HPV18 genome integrated into the cervical carcinoma cell line HeLa. Transcription analysis revealed transcripts of heterogeneous sizes, spanning the distal early region (E2S4E5) of the HPV6 genome, as happens in vivo in Condylomata acuminata, although in these genital lesions the HPV6 genome is maintained as a non-integrated episome.
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PMID:Integration and transcription of human papillomavirus type 6 recombinant DNA in mouse cells. 282 59