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PMID: 3263510 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Characterization of cellular factors that interact with the human T-cell leukemia virus type I p40x-responsive 21-base-pair sequence.

Journal of virology ·Vol. 62 ·No. 12 ·1988-12-00 ·Pages 4499-509

Jeang KT, Boros I, Brady J, Radonovich M, Khoury G

Abstract

Transcriptional activation of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat (LTR) by viral protein p40x requires a 21-base-pair (bp) sequence which is repeated three times within the LTR. This sequence contains a core octanucleotide (TGACGTCT) which has been attributed to be a cyclic-AMP (cAMP)-responsive element. We demonstrate here that the HTLV-I LTR can be specifically stimulated by cAMP regulators and have identified four proteins in HeLa cells that bind to the HTLV-I 21-bp sequence. We correlated the in vitro binding and transcriptional activity of one of these cellular factors (Mr, 180,000) to the trans-activation of the HTLV-I LTR by p40x. Point mutations were generated within the cAMP octanucleotide of the HTLV-I 21-bp sequence that simultaneously abolished biological responsiveness to trans-activation by p40x and to stimulation by cAMP. We found that these mutations also eliminated the binding of the 180-kilodalton HeLa factor to the HTLV-I 21-bp element. In the absence of a demonstrable DNA-binding property for p40x, we hypothesize that cellular proteins are involved, possibly through signal transduction pathways, in its trans-activation of responsive promoters.

MeSH Terms
Base Sequence DNA Probes DNA, Viral/genetics Electrophoresis, Polyacrylamide Gel Genes, Viral HTLV-I Antigens/genetics HeLa Cells Human T-lymphotropic virus 1/genetics Humans Molecular Sequence Data Mutation Repetitive Sequences, Nucleic Acid Trans-Activators Transcription Factors/genetics Transcription, Genetic
Chemicals
DNA Probes DNA, Viral HTLV-I Antigens Trans-Activators Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Jeang K T
Laboratory of Molecular Virology, National Cancer Institute, Bethesda, Maryland 20892.
Boros I
Brady J
Radonovich M
Khoury G
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
1988-12-00
Pages
4499-509
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC253560
Subset
IM
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