Different arrangement of human papillomavirus E2 binding sites distinguishes cutaneous types from those associated with mucosal lesions.
High-risk-type human papillomavirus DNA sequences are found in a high percentage of carcinomas from the uterine-cervix, with the viral E1-E2 gene region usually disrupted and the E6 and E7 oncoproteins consistently expressed. The E2 protein is known to repress early transcription from genital HPV promoters having a proximal E2 binding site (E2BS) close to the TATA box. On the contrary, the E2 protein activates cutaneous early promoters having a longer distance between these sites. Using an in vivo approach we analyzed the regulation, by the BPV-1E2 protein, of a natural HPV-18 promoter where proximal E2BS were placed at variable positions relative to the TATA box, and of heterologous promoters where E2BS was placed upstream of any other known DNA-binding elements. Our results confirm that the E2 protein represses or activates HPV early gene transcription depending on the distance between the TATA box and the proximal E2BS.
Garrido-Guerrero
E
E
Laboratorio de Inmunología UMF, ENEP Iziacala, UNAM, Tlalnepantla, Edo de México.
Carrillo
E
E
Guido
M
M
Zamorano
R
R
García-Carranca
A
A
Gariglio
P
P
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D052688:Bovine papillomavirus 1 / Q000235:genetics; D019556:COS Cells; D002277:Carcinoma / Q000821:virology; D002417:Cattle; D004274:DNA, Recombinant / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D015967:Gene Expression Regulation, Viral; D006801:Humans; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000821:virology*; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017193:Skin Diseases, Viral / Q000821:virology*; D016385:TATA Box; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014412:Tumor Virus Infections / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000821:virology; D002575:Uterine Cervicitis / Q000821:virology*
D004274:DNA, Recombinant; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D014157:Transcription Factors; C069102:oncogene protein E2, Human papillomavirus type 18