Cellular transcription factors regulate human papillomavirus type 16 gene expression by binding to a subset of the DNA sequences recognized by the viral E2 protein

Human papillomavirus type 16 (HPV-16) is a DNA tumour virus that has been implicated in the development of cervical cancer. The HPV-16 E2 protein binds to four sites that are present upstream of the viral P97 promoter and regulates transcription of the E6 and E7 oncogenes. Here, it is shown that cellular transcription factors bind to two of these E2 sites. One cellular E2 site-binding factor, which is here named CEF-1, binds tightly to E2 site 1. CEF-2, an unrelated cellular E2 site-binding factor, binds tightly to E2 site 3. Transient transfection studies performed in the absence of the E2 protein showed that mutations that blocked the binding of CEF-1 to E2 site 1 or CEF-2 to E2 site 3 significantly reduced P97 promoter activity. Further characterization of CEF-1 indicated that this factor has not previously been identified and that CEF-1 and E2 competed for binding at E2 site 1.