University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Medicine; Program in Immunology and Virology

Publication Date

2-2013

Document Type

Article

Subjects

Acetylation; Animals; Bovine papillomavirus 1; Cattle; Cell Line; DNA-Binding Proteins; *Gene Expression Regulation, Viral; *Host-Pathogen Interactions; Lysine; *Transcription, Genetic; Viral Proteins; p300-CBP Transcription Factors

Disciplines

Immunopathology | Molecular Genetics | Virology

Abstract

The p300, CBP, and pCAF lysine acetyltransferase (KAT) proteins have been reported to physically interact with bovine (BPV) and human (HPV) papillomavirus E2 proteins. While overexpression of these KAT proteins enhances E2-dependent transcription, the mechanism has not been determined. Using RNA interference (RNAi) to deplete these factors, we demonstrated that E2 transcriptional activity requires physiological levels of p300, CBP, and pCAF. Each protein appears to have a unique function in E2-dependent transcription, since overexpression of one KAT failed to compensate for RNAi knockdown of another KAT. Using an in vitro acetylation assay, we identified highly conserved lysines that are targeted by p300 for acetylation. The conservative changes of lysines at positions 111 and 112 to arginine were of particular interest. The K111R and the K111R/K112R mutants showed reduced transcriptional activity that was not responsive to p300 overexpression, while the K112R mutant retained activity. p300 and CBP were detected at the viral promoter; however, pCAF was not. We propose a model by which E2 transcriptional activity is controlled by p300-mediated acetylation of lysine 111. This model represents a novel mechanism regulating papillomavirus gene expression.

Rights and Permissions

Citation: J Virol. 2013 Feb;87(3):1497-507. doi: 10.1128/JVI.02771-12. Epub 2012 Nov 14. Link to article on publisher's site

Comments

Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.

Co-author Edward Quinlan is a student in the Immunology and Virology Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Journal of virology

PubMed ID

23152516

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