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

Document Type

Article

Publication Date

11-22-2002

Publication Title

The Journal of biological chemistry

Keywords

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

Abstract

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.

Clinical Institute

Neurosciences (Brain & Spine)

Department

Neurosciences

Comments

Samuel Hou is affiliated with Providence St. Joseph Health.

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