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PMID: 2828035 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The upstream regulatory region of the human papilloma virus-16 contains an E2 protein-independent enhancer which is specific for cervical carcinoma cells and regulated by glucocorticoid hormones.

The EMBO journal ·Vol. 6 ·No. 12 ·1987-12-01 ·Pages 3735-43

Gloss B, Bernard HU, Seedorf K, Klock G

Abstract

The upstream regulatory region of the human papilloma virus-16 (HPV-16) genomic DNA contains a sequence element with a large degree of homology to the partially palindromic sequence GGTACANNNTGTTCT, which is the consensus sequence of the glucocorticoid responsive elements of known genes regulated by this steroid hormone. DNase I and dimethylsulfate protection experiments reveal the binding of this sequence by rat glucocorticoid receptor protein. A 400-bp DNA segment centrally containing this sequence confers strong inducibility by dexamethasone to the promoter p97 of HPV-16 and to the Herpes simplex virus thymidine kinase promoter, as judged by chloramphenicol acetyltransferase activity and RNase protection assays. The same DNA segment, that does not contain the consensus sequences of all papilloma viruses relevant for E2 protein-mediated transcription enhancement, functions in an enhancer-like fashion in addition to its glucocorticoid responsive action. This hormone-independent transcription enhancement is absent in human MCF7 cells, but is strong in human HeLa cells where the combined activity of the constitutive and the steroid hormone-dependent enhancer elements stimulate transcription by a factor of 500. This cell type specificity of the HPV-16 enhancer may be responsible for the tissue tropism of the virus. These observations and the presence of numerous homologies to known enhancers of cellular and viral genes suggest a complex pattern of activation of the human papilloma virus-16 promoters.

MeSH Terms
Base Sequence Cell Line DNA-Binding Proteins Dexamethasone/pharmacology Dihydrotestosterone/pharmacology Enhancer Elements, Genetic/drug effects Female Genes/drug effects Genes, Regulator/drug effects Genes, Viral/drug effects Humans Molecular Sequence Data Oncogene Proteins, Viral/genetics Papillomaviridae/drug effects,genetics Promoter Regions, Genetic Sequence Homology, Nucleic Acid Simplexvirus/genetics Transcription, Genetic/drug effects Transfection Uterine Cervical Neoplasms/genetics
Chemicals
DNA-Binding Proteins E2 protein, Human papillomavirus type 16 Oncogene Proteins, Viral Dihydrotestosterone Dexamethasone
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Gloss B
German Cancer Research Center, Institute for Cell and Tumor Biology, Heidelberg, FRG.
Bernard H U
Seedorf K
Klock G
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1987-12-01
Pages
3735-43
Language
English
Region
England
NLM ID
8208664
PMCID
PMC553844
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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