The E1E4 protein of human papillomavirus type 16 associates with a putative RNA helicase through sequences in its C terminus.
Elston, Robert C
Griffin, Heather M
Stacey, Simon N
AffiliationDivision of Virology, National Institute for Medical Research, Mill Hill, London, United Kingdom. email@example.com
MetadataShow full item record
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.
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.
JournalJournal of Virology
- Differentiation-dependent expression of E1--E4 proteins in cell lines maintaining episomes of human papillomavirus type 31b.
- Authors: Pray TR, Laimins LA
- Issue date: 1995 Jan 10
- The human papillomavirus type 11 E1E4 protein is phosphorylated in genital epithelium.
- Authors: Bryan JT, Han A, Fife KH, Brown DR
- Issue date: 2000 Mar 15
- Functional analysis of the human papillomavirus type 16 E1=E4 protein provides a mechanism for in vivo and in vitro keratin filament reorganization.
- Authors: Wang Q, Griffin H, Southern S, Jackson D, Martin A, McIntosh P, Davy C, Masterson PJ, Walker PA, Laskey P, Omary MB, Doorbar J
- Issue date: 2004 Jan
- Analysis of HPV1 E4 complexes and their association with keratins in vivo.
- Authors: Doorbar J, Medcalf E, Napthine S
- Issue date: 1996 Apr 1
- Identification of a G(2) arrest domain in the E1 wedge E4 protein of human papillomavirus type 16.
- Authors: Davy CE, Jackson DJ, Wang Q, Raj K, Masterson PJ, Fenner NF, Southern S, Cuthill S, Millar JB, Doorbar J
- Issue date: 2002 Oct