Characterization of cellular factors that interact with the human T-cell leukemia virus type I p40(X)-responsive 21-base-pair sequence

K. T. Jeang, I. Boros, J. Brady, M. Radonovich, G. Khoury

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Transcriptional activation of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat (LTR) by viral protein p40(X) 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 (M(r), 180,000) to the trans-activation of the HTLV-I LTR by p40(X). Point mutations were generated within the cAMP octanucleotide of the HTLV-I 21-bp sequence that simultaneously abolished biological responsiveness to trans-activation by p40(X) 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 p40(X), we hypothesize that cellular proteins are involved, possibly through signal transduction pathways, in its trans-activation of responsive promoters.

Original languageEnglish
Pages (from-to)4499-4509
Number of pages11
JournalJournal of Virology
Volume62
Issue number12
Publication statusPublished - 1988

Fingerprint

Primate T-lymphotropic virus 1
Human T-lymphotropic virus 1
Base Pairing
terminal repeat sequences
Terminal Repeat Sequences
cyclic AMP
transcriptional activation
Cyclic AMP
binding properties
viral proteins
Viral Proteins
point mutation
HeLa Cells
Point Mutation
Transcriptional Activation
signal transduction
adjuvant P40
Signal Transduction
Proteins
proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Characterization of cellular factors that interact with the human T-cell leukemia virus type I p40(X)-responsive 21-base-pair sequence. / Jeang, K. T.; Boros, I.; Brady, J.; Radonovich, M.; Khoury, G.

In: Journal of Virology, Vol. 62, No. 12, 1988, p. 4499-4509.

Research output: Contribution to journalArticle

@article{f138a667940a4f25893b1d60d8d2d47d,
title = "Characterization of cellular factors that interact with the human T-cell leukemia virus type I p40(X)-responsive 21-base-pair sequence",
abstract = "Transcriptional activation of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat (LTR) by viral protein p40(X) 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 (M(r), 180,000) to the trans-activation of the HTLV-I LTR by p40(X). Point mutations were generated within the cAMP octanucleotide of the HTLV-I 21-bp sequence that simultaneously abolished biological responsiveness to trans-activation by p40(X) 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 p40(X), we hypothesize that cellular proteins are involved, possibly through signal transduction pathways, in its trans-activation of responsive promoters.",
author = "Jeang, {K. T.} and I. Boros and J. Brady and M. Radonovich and G. Khoury",
year = "1988",
language = "English",
volume = "62",
pages = "4499--4509",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - Characterization of cellular factors that interact with the human T-cell leukemia virus type I p40(X)-responsive 21-base-pair sequence

AU - Jeang, K. T.

AU - Boros, I.

AU - Brady, J.

AU - Radonovich, M.

AU - Khoury, G.

PY - 1988

Y1 - 1988

N2 - Transcriptional activation of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat (LTR) by viral protein p40(X) 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 (M(r), 180,000) to the trans-activation of the HTLV-I LTR by p40(X). Point mutations were generated within the cAMP octanucleotide of the HTLV-I 21-bp sequence that simultaneously abolished biological responsiveness to trans-activation by p40(X) 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 p40(X), we hypothesize that cellular proteins are involved, possibly through signal transduction pathways, in its trans-activation of responsive promoters.

AB - Transcriptional activation of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat (LTR) by viral protein p40(X) 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 (M(r), 180,000) to the trans-activation of the HTLV-I LTR by p40(X). Point mutations were generated within the cAMP octanucleotide of the HTLV-I 21-bp sequence that simultaneously abolished biological responsiveness to trans-activation by p40(X) 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 p40(X), we hypothesize that cellular proteins are involved, possibly through signal transduction pathways, in its trans-activation of responsive promoters.

UR - http://www.scopus.com/inward/record.url?scp=0024209354&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024209354&partnerID=8YFLogxK

M3 - Article

C2 - 3263510

AN - SCOPUS:0024209354

VL - 62

SP - 4499

EP - 4509

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 12

ER -