Transcriptional activation of the human papillomavirus-16 P97 promoter by an 88-nucleotide enhancer containing distinct cell-dependent and AP-1-responsive modules

T P Cripe; A Alderborn; R D Anderson; S Parkkinen; P Bergman; T H Haugen; U Pettersson; L P Turek

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Journal article

Transcriptional activation of the human papillomavirus-16 P97 promoter by an 88-nucleotide enhancer containing distinct cell-dependent and AP-1-responsive modules

T P Cripe, A Alderborn, R D Anderson, S Parkkinen, P Bergman, T H Haugen, U Pettersson and L P Turek

The New biologist, Vol.2(5), pp.450-463

05/1990

PMID: 1963084

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Abstract

The P97 promoter upstream of the oncogenic early genes of human papillomavirus (HPV)-16 is active in keratinocytes and in cervical carcinoma cells due to a 5' keratinocyte-dependent cis enhancer. In this study, we have mapped the main enhancer activity to an 88-nucleotide (nt) fragment composed of multiple cis elements. A 63-nt promoter-proximal enhancer core was sufficient for P97 activation in a human keratinocytic cell line, HaCaT, and in cervical carcinoma cells. Although the enhancer functioned poorly in hepatoma cells or in fibroblasts, nuclear extracts from different cells protected similar cis elements from DNase I digestion. Two protected half-palindromic NF-I/CTF sites within the 63-nt core were necessary for its function; one represents a "cytokeratin element" (CK), a previously described 8-nt sequence shared with cytokeratin gene promoters. Both sites formed complexes of the same apparent size and relative binding affinity with NF-I/CTF-like factor(s) present in all cells tested. Although cell-dependent P97 activation could be determined by similar, yet distinct NF-I/CTF-like proteins, adjacent cis elements in the enhancer core were also required for function, and may thus interact with additional transcription factors. A 25-nt distal module with two AP-1 sites increased enhancer activity and cooperated with cis elements of the proximal core. Each AP-1 site as well as a third AP-1 site near the promoter bound c-Jun and Jun/Fos in vitro, and was activated by c-Jun and c-Fos in transfections. In addition to cell type-dependent activation, HPV-16 P97 transcription may therefore respond to growth factors and oncogene products via the AP-1 pathway.

Consensus Sequence

Promoter Regions, Genetic

Humans

Molecular Sequence Data

Proto-Oncogene Proteins - genetics

NFI Transcription Factors

Transcription Factors - genetics

DNA-Binding Proteins - genetics

RNA, Messenger - metabolism

Papillomaviridae - genetics

CCAAT-Enhancer-Binding Proteins

Nuclear Proteins

Proto-Oncogene Proteins c-fos

DNA, Viral - chemistry

Gene Expression Regulation, Viral

Keratinocytes - metabolism

Base Sequence

TATA Box

Y-Box-Binding Protein 1

Transcription, Genetic

Tumor Cells, Cultured

Proto-Oncogene Proteins c-jun

Details

Title: Subtitle: Transcriptional activation of the human papillomavirus-16 P97 promoter by an 88-nucleotide enhancer containing distinct cell-dependent and AP-1-responsive modules
Creators: T P Cripe - Department of Pathology, Veterans Administration Medical Center, Iowa City, IA
A Alderborn
R D Anderson
S Parkkinen
P Bergman
T H Haugen
U Pettersson
L P Turek
Resource Type: Journal article
Publication Details: The New biologist, Vol.2(5), pp.450-463
Publisher: United States
PMID: 1963084
ISSN: 1043-4674
Grant note: CA-49912 / NCI NIH HHS
Language: English
Date published: 05/1990
Academic Unit: Pathology
Record Identifier: 9984047673402771

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