The promoter of a novel human papillomavirus (HPV77) associated with skin cancer displays UV responsiveness, which is mediated through a consensus p53 binding sequence.
An aetiological role has been proposed for human papillomavirus (HPV) in skin carcinogenesis within the immunosuppressed patient population. To examine this possibility, we have focused on an HPV type that, to date, has been identified only in the cutaneous lesions of renal transplant recipients despite a high degree of sequence homology with other HPVs commonly found in warts in the general population. We report that the non-coding region of this virus, HPV type 77, contains a consensus binding site for the tumour suppressor protein p53, and we show by gel-retardation analysis that this sequence does indeed bind p53. Furthermore, using reporter gene assays, we demonstrate that HPV77 promoter activity is stimulated by UV radiation and that this response is mediated through the p53 binding site. This is the first report of a p53-dependent positive response element within a viral genome. Our results suggest a possible novel mechanism by which specific types of HPV might act as cofactors with UV radiation in cutaneous transformation.
Purdie
K J
KJ
ICRF Skin Tumour Laboratory, Centre for Cutaneous Research, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, 2 Newark Street, London E1 2AT, UK.
Pennington
J
J
Proby
C M
CM
Khalaf
S
S
de Villiers
E M
EM
Leigh
I M
IM
Storey
A
A
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D003043:Cocarcinogenesis; D016384:Consensus Sequence; D004279:DNA, Viral; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D009381:Neoplasms, Radiation-Induced / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid; D012878:Skin Neoplasms / Q000821:virology*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*; D014466:Ultraviolet Rays
D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53