Human papillomavirus replication regulation by acetylation of a conserved lysine in the E2 protein

Yanique Thomas, Elliot Androphy

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The papillomavirus (PV) E2 protein is a sequence-specific DNA binding protein that recruits cellular factors to its genome in infected epithelial cells. E2 also binds to and loads the viral E1 DNA helicase at the origin of replication. Posttranslational modifications (PTMs) of PV E2 have been identified as potential regulators of E2 functions. We recently reported lysine 111 (K111) as a target of p300 acetylation in bovine PV (BPV). The di-lysines at 111 and 112 are conserved in almost all papillomaviruses. We pursued a mutational approach to query the functional significance of lysine in human PV (HPV) E2. Amino acid substitutions that prevent acetylation, including arginine, were unable to stimulate transcription and E1-mediated DNA replication. The arginine K111 mutant retained E2 transcriptional repression, nuclear localization, DNA and chromatin binding, and association with E2 binding partners involved in PV transcription and replication. While the replication-defective E2-K111R mutant recruited E1 to the viral replication origin, surprisingly, unwinding of the duplex DNA did not occur. In contrast, the K111 glutamine (K111Q) mutant increased origin melting and stimulated replication compared to wild-type E2. These experiments reveal a novel activity of E2 necessary for denaturing the viral origin that likely depends on acetylation of highly conserved lysine 111.

Original languageEnglish (US)
Article numbere01912-17
JournalJournal of Virology
Volume92
Issue number3
DOIs
StatePublished - Feb 1 2018

Fingerprint

Papillomaviridae
acetylation
Acetylation
Lysine
lysine
Replication Origin
replication origin
Arginine
Proteins
proteins
mutants
arginine
DNA Helicases
transcription (genetics)
Bovine papillomavirus
DNA helicases
DNA
Viral DNA
DNA-Binding Proteins
Amino Acid Substitution

Keywords

  • Acetylation
  • Lysine
  • Papillomavirus
  • Viral replication

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Human papillomavirus replication regulation by acetylation of a conserved lysine in the E2 protein. / Thomas, Yanique; Androphy, Elliot.

In: Journal of Virology, Vol. 92, No. 3, e01912-17, 01.02.2018.

Research output: Contribution to journalArticle

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