Two AP1 sites binding JunB are essential for human papillomavirus type 18 transcription in keratinocytes.
The activity and epithelial tropism of the human papillomavirus type 18 P105 early promoter, which directs the synthesis of the E6 and E7 transforming genes, are controlled by cis elements included in the viral long control region. To identify potential cellular regulators of this promoter, we mutagenized one or both of the 5'-TGACTAA-3' cis elements capable of interacting with the AP1 transcription factor, which is composed either of homodimers or heterodimers of the Jun products or of heterodimers of Jun and Fos. Mutation of both elements completely abolished P105 promoter activity in human keratinocytes. We show that either AP1 site can interact efficiently in vitro with any of the three different Jun products as heterodimers with c-Fos. However, in nuclear extracts prepared from human keratinocytes, JunB was the predominant Jun component bound to the DNA probe containing this cis element. These results implicate JunB as an important factor in human papillomavirus type 18 transcription in keratinocytes and strongly suggest a potential role of this Jun gene product in the tissue-specific transcription of the genital papillomaviruses.
Thierry
F
F
Unité des Virus Oncogènes, UA1149 CNRS, Institut Pasteur, Paris, France.
Spyrou
G
G
Yaniv
M
M
Howley
P
P
D001483:Base Sequence; D002277:Carcinoma / Q000382:microbiology; D002467:Cell Nucleus / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D015967:Gene Expression Regulation, Viral; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000382:microbiology; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000382:microbiology; D027383:Papillomaviridae / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000382:microbiology
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun