The E1E4 protein of human papillomavirus type 16 associates with a putative RNA helicase through sequences in its C terminus.

2.50
Hdl Handle:
http://hdl.handle.net/10541/90140
Title:
The E1E4 protein of human papillomavirus type 16 associates with a putative RNA helicase through sequences in its C terminus.
Authors:
Doorbar, John; Elston, Robert C; Napthine, Sawsan; Raj, Kenneth; Medcalf, Elizabeth; Jackson, Deborah; Coleman, Nick; Griffin, Heather M; Masterson, Philip; Stacey, Simon N; Mengistu, Yohannes; Dunlop, Julia
Abstract:
Human 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.
Affiliation:
Division of Virology, National Institute for Medical Research, Mill Hill, London, United Kingdom. jdoorba@nimr.mrc.ac.uk
Citation:
The 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.
Journal:
Journal of Virology
Issue Date:
Nov-2000
URI:
http://hdl.handle.net/10541/90140
PubMed ID:
11024137
Type:
Article
Language:
en
ISSN:
0022-538X
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorDoorbar, Johnen
dc.contributor.authorElston, Robert Cen
dc.contributor.authorNapthine, Sawsanen
dc.contributor.authorRaj, Kennethen
dc.contributor.authorMedcalf, Elizabethen
dc.contributor.authorJackson, Deborahen
dc.contributor.authorColeman, Nicken
dc.contributor.authorGriffin, Heather Men
dc.contributor.authorMasterson, Philipen
dc.contributor.authorStacey, Simon Nen
dc.contributor.authorMengistu, Yohannesen
dc.contributor.authorDunlop, Juliaen
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.en
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

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