Transcriptional activity among high and low risk human papillomavirus E2 proteins correlates with E2 DNA binding

J Biol Chem. 2002 Nov 22;277(47):45619-29. doi: 10.1074/jbc.M206829200. Epub 2002 Sep 17.


The full-length E2 protein, encoded by human papillomaviruses (HPVs), is a sequence-specific transcription factor found in all HPVs, including cancer-causing high risk HPV types 16 and 18 and wart-inducing low risk HPV types 6 and 11. To investigate whether E2 proteins encoded by high risk HPVs may function differentially from E2 proteins encoded by low risk HPVs and animal papillomaviruses, we conducted comparative DNA-binding and transcription studies using electrophoretic mobility shift assays and cell-free transcription systems reconstituted with purified general transcription factors, cofactor, RNA polymerase II, and with E2 proteins encoded by HPV-16, HPV-18, HPV-11, and bovine papillomavirus type 1 (BPV-1). We found that although different types of E2 proteins all exhibited transactivation and repression activities, depending on the sequence context of the E2-binding sites, HPV-16 E2 shows stronger transcription activity and greater DNA-binding affinity than those displayed by the other E2 proteins. Surprisingly, HPV-18 E2 behaves more similarly to BPV-1 E2 than HPV-16 E2 in its functional properties. Our studies thus categorize HPV-18 E2 and BPV-1 E2 in the same protein family, a finding consistent with the available E2 structural data that separate the closely related HPV-16 and HPV-18 E2 proteins but classify together the more divergent BPV-1 and HPV-18 E2 proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bovine papillomavirus 1 / genetics
  • Bovine papillomavirus 1 / metabolism
  • Cell-Free System
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism*
  • Papillomaviridae / genetics*
  • Papillomaviridae / metabolism
  • Promoter Regions, Genetic
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Risk Factors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*


  • DNA-Binding Proteins
  • E2 protein, Human papillomavirus type 11
  • E2 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • Viral Proteins
  • oncogene protein E2, Human papillomavirus type 18
  • DNA