The short arm of chromosome 11 likely is involved in the regulation of the human papillomavirus type 16 early enhancer-promoter and in the suppression of the transforming activity of the viral DNA.
Loci on the short arm of chromosome 11 between 11p11 and 11p15 likely are involved directly or indirectly in the regulation of the HPV-16 enhancer-promoter strength and this may contribute to the control of the level of viral early gene expression. Transient expression assays have shown that the HPV-16 enhancer-promoter functions much stronger in fibroblasts in which this region of chromosome 11 (del-11 cells) is deleted than in normal diploid human embryonic fibroblasts. The differential regulation of the HPV-16 long control region may be due either to the presence or activity of a cellular transcription factor which up-regulates HPV-16 early gene expression in del-11 cells or to a factor which down-regulates expression in diploid cells. Since the HPV-16 enhancer containing fragment (nt 7003 to nt 57) in combination with the SV40 promoter functions equally well in del-11 cells as in diploid cells a target of this factor likely is located in the putative HPV-16 early promoter region. The relative resistance of diploid human embryonic fibroblasts to HPV-16 induced transformation could be explained by the inactivity of the HPV-16 early promoter as these cells could be transformed by HPV-16 DNA constructs in which the early gene expression was driven from a heterologous enhancer-promoter. These results may indicate that loci on the short arm could suppress HPV-16-induced transformation by down-regulating the activity of the viral early promoter.
Smits
P H
PH
Department of Medical Microbiology, University of Amsterdam, The Netherlands.
Smits
H L
HL
Jebbink
M F
MF
ter Schegget
J
J
D002478:Cells, Cultured; D002880:Chromosomes, Human, Pair 11 / Q000502:physiology*; D004279:DNA, Viral / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005347:Fibroblasts; D006801:Humans; D009154:Mutation; D027383:Papillomaviridae / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012367:RNA, Viral / Q000032:analysis; D014162:Transfection; D014170:Transformation, Genetic
D004279:DNA, Viral; D012367:RNA, Viral