Characterization of a nuclear factor, papilloma enhancer binding factor-1, that binds the long control region of human papillomavirus type 16 and contributes to enhancer activity.
Human papillomavirus type-16 (HPV-16) is an epitheliotropic DNA tumor virus associated with the development of cervical carcinoma. The expression of HPV-16 early genes is driven by a cell-type-specific enhancer located in the long control region of the viral genome. We identified an element within the HPV-16 minimal enhancer that has enhancer activity and binds a nuclear factor, designated papillomavirus enhancer binding factor-1 (PEF-1). The element (called-FP-F by us and fp5e by Gloss et al. (EMBO J 6:3735-3743, 1987)) was originally identified as a footprint by DNase I protection experiments. The PEF-1 binding site is centered around a CCAAT box-like CCAAC element. Introduction of A-->T transversions into the CCAAC element of fp5e abolished binding of PEF-1 and concomitantly abolished enhancer function. fp5e resembles binding sites for the transcriptional activators CTF/NF-1 and AP-2; however, we showed that neither of these factors interacted with this element. PEF-1 has an apparent molecular weight of about 110 kDa, and we propose that it is a novel factor involved in the transcriptional activation of HPV-16 gene expression.
Cuthill
S
S
Beatson Institute for Cancer Research, CRC Beatson Laboratories, Glasgow, United Kingdom.
Sibbet
G J
GJ
Campo
M S
MS
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004742:Enhancer Elements, Genetic; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; C486169:Ybx1 protein, rat