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dc.contributor.authorDoorbar, John
dc.contributor.authorElston, Robert C
dc.contributor.authorNapthine, Sawsan
dc.contributor.authorRaj, Kenneth
dc.contributor.authorMedcalf, Elizabeth
dc.contributor.authorJackson, Deborah
dc.contributor.authorColeman, Nick
dc.contributor.authorGriffin, Heather M
dc.contributor.authorMasterson, Philip
dc.contributor.authorStacey, Simon N
dc.contributor.authorMengistu, Yohannes
dc.contributor.authorDunlop, Julia
dc.date.accessioned2010-01-20T15:03:44Z
dc.date.available2010-01-20T15:03:44Z
dc.date.issued2000-11
dc.identifier.citationThe E1E4 protein of human papillomavirus type 16 associates with a putative RNA helicase through sequences in its C terminus. 2000, 74 (21):10081-95 J. Virol.en
dc.identifier.issn0022-538X
dc.identifier.pmid11024137
dc.identifier.urihttp://hdl.handle.net/10541/90140
dc.description.abstractHuman papillomavirus type 16 (HPV16) infects cervical epithelium and is associated with the majority of cervical cancers. The E1E4 protein of HPV16 but not those of HPV1 or HPV6 was found to associate with a novel member of the DEAD box protein family of RNA helicases through sequences in its C terminus. This protein, termed E4-DBP (E4-DEAD box protein), has a molecular weight of 66,000 (66K) and can shuttle between the nucleus and the cytoplasm. It binds to RNA in vitro, including the major HPV16 late transcript (E1E4. L1), and has an RNA-independent ATPase activity which can be partially inhibited by E1E4. E4-DBP was detectable in the cytoplasm of cells expressing HPV16 E1E4 (in vivo and in vitro) and could be immunoprecipitated as an E1E4 complex from cervical epithelial cell lines. In cell lines lacking cytoplasmic intermediate filaments, loss of the leucine cluster-cytoplasmic anchor region of HPV16 E1wedgeE4 resulted in both proteins colocalizing exclusively to the nucleoli. Two additional HPV16 E1E4-binding proteins, of 80K and 50K, were identified in pull-down experiments but were not recognized by antibodies to E4-DBP or the conserved DEAD box motif. Sequence analysis of E4-DBP revealed homology in its E4-binding region with three Escherichia coli DEAD box proteins involved in the regulation of mRNA stability and degradation (RhlB, SrmB, and DeaD) and with the Rrp3 protein of Saccharomyces cerevisiae, which is involved in ribosome biogenesis. The synthesis of HPV16 coat proteins occurs after E1E4 expression and genome amplification and is regulated at the level of mRNA stability and translation. Identification of E4-DBP as an HPV16 E1E4-associated protein indicates a possible role for E1E4 in virus synthesis.
dc.language.isoenen
dc.subjectCultured Tumour Cellsen
dc.subjectTumour Virus Infectionsen
dc.subject.meshCell Nucleus
dc.subject.meshCytoplasm
dc.subject.meshDEAD-box RNA Helicases
dc.subject.meshGene Expression Regulation, Viral
dc.subject.meshHela Cells
dc.subject.meshHumans
dc.subject.meshMolecular Sequence Data
dc.subject.meshNuclear Proteins
dc.subject.meshOncogene Proteins, Fusion
dc.subject.meshPapillomaviridae
dc.subject.meshPapillomavirus Infections
dc.subject.meshRNA Helicases
dc.subject.meshRNA, Messenger
dc.subject.meshRibosomes
dc.subject.meshSequence Analysis, DNA
dc.subject.meshSequence Homology, Amino Acid
dc.subject.meshTumor Cells, Cultured
dc.subject.meshTumor Virus Infections
dc.subject.meshTwo-Hybrid System Techniques
dc.subject.meshViral Proteins
dc.titleThe E1E4 protein of human papillomavirus type 16 associates with a putative RNA helicase through sequences in its C terminus.en
dc.typeArticleen
dc.contributor.departmentDivision of Virology, National Institute for Medical Research, Mill Hill, London, United Kingdom. jdoorba@nimr.mrc.ac.uken
dc.identifier.journalJournal of Virologyen
html.description.abstractHuman papillomavirus type 16 (HPV16) infects cervical epithelium and is associated with the majority of cervical cancers. The E1E4 protein of HPV16 but not those of HPV1 or HPV6 was found to associate with a novel member of the DEAD box protein family of RNA helicases through sequences in its C terminus. This protein, termed E4-DBP (E4-DEAD box protein), has a molecular weight of 66,000 (66K) and can shuttle between the nucleus and the cytoplasm. It binds to RNA in vitro, including the major HPV16 late transcript (E1E4. L1), and has an RNA-independent ATPase activity which can be partially inhibited by E1E4. E4-DBP was detectable in the cytoplasm of cells expressing HPV16 E1E4 (in vivo and in vitro) and could be immunoprecipitated as an E1E4 complex from cervical epithelial cell lines. In cell lines lacking cytoplasmic intermediate filaments, loss of the leucine cluster-cytoplasmic anchor region of HPV16 E1wedgeE4 resulted in both proteins colocalizing exclusively to the nucleoli. Two additional HPV16 E1E4-binding proteins, of 80K and 50K, were identified in pull-down experiments but were not recognized by antibodies to E4-DBP or the conserved DEAD box motif. Sequence analysis of E4-DBP revealed homology in its E4-binding region with three Escherichia coli DEAD box proteins involved in the regulation of mRNA stability and degradation (RhlB, SrmB, and DeaD) and with the Rrp3 protein of Saccharomyces cerevisiae, which is involved in ribosome biogenesis. The synthesis of HPV16 coat proteins occurs after E1E4 expression and genome amplification and is regulated at the level of mRNA stability and translation. Identification of E4-DBP as an HPV16 E1E4-associated protein indicates a possible role for E1E4 in virus synthesis.


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