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

153 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
DOIs
Publication statusPublished - Jan 1 1988

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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