Type

Journal Article

Authors

Stefan Schwartz
Göran Akusjärvi
Helen Lambkin
Fergus Ryan
Joanna Fay
Margaret Rush
Monica Somberg

Subjects

Biochemistry

Topics
splicing oncology e4orf4 adenovirus asf sf2 genetic processes hpv late gene expression hpv

Adenovirus E4orf4 induces HPV-16 late L1 mRNA production (2009)

Abstract The adenovirus E4orf4 protein regulates the switch from early to late gene expression during the adenoviral replication cycle. Here we report that overexpression of adenovirus E4orf4 induces human papillomavirus type 16 (HPV-16) late gene expression from subgenomic expression plasmids. E4orf4 specifically overcomes the negative effects of two splicing silencers at the two late HPV-16 splice sites SD3632 and SA5639. This results in the production of HPV-16 spliced L1 mRNAs. We show that the interaction of E4orf4 with protein phosphatase 2A (PP2A) is necessary for induction of HPV-16 late gene expression. Also an E4orf4 mutant that fails to bind the cellular splicing factor ASF/SF2 fails to induce L1 mRNA production. Collectively, these results suggest that dephosphorylation of SR proteins by E4orf4 activates HPV-16 late gene expression. Indeed, a mutant ASF/SF2 protein in which the RS-domain had been deleted could itself induce HPV-16 late gene expression, whereas wild type ASF/SF2 could not.
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Full list of authors on original publication

Stefan Schwartz, Göran Akusjärvi, Helen Lambkin, Fergus Ryan, Joanna Fay, Margaret Rush, Monica Somberg

Experts in our system

1
Helen Lambkin
Dublin Institute of Technology
Total Publications: 23
 
2
Fergus Ryan
Dublin Institute of Technology
Total Publications: 44
 
3
Joanna Fay
Royal College of Surgeons in Ireland
Total Publications: 24