The human T-cell leukemia virus-1 transcriptional activator tax enhances cAMP-responsive element-binding protein (CREB) binding activity through interactions with the DNA minor groove

James Lundblad, Roland P S Kwok, Megan E. Laurance, Mary S. Huang, Jane P. Richards, Richard G. Brennan, Richard Goodman

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Tax-1, the transcriptional activation protein of human T-cell leukemia virus-1, increases transcription from the human T-cell leukemia virus-1 long terminal repeat and specific cellular promoters through interactions with cellular DNA-binding proteins. The Tax response elements (TxREs) of the long terminal repeat resemble cAMP response elements (CREs), the target of cAMP responsive element-binding protein (CREB). CREB binds the TxRE with reduced affinity; however, the interaction is specifically enhanced by Tax. Using a fluorescence quenching method, we determined that CREB dimerizes in the absence of DNA, and that Tax does not enhance dimerization. DNA footprinting of the TxRE with 1,10-phenanthroline-copper complex demonstrates that Tax contacts DNA and extends the footprint of CREB to GC-rich sequences flanking the core CRE-like element. The minor groove-binding drug chromomycin A3, but not distamycin A, disrupted Tax-enhanced CREB binding to the TxRE. Substitution of the guanine-rich sequences flanking the core of the TxRE with inosine residues also blocked the Tax effect. Finally, the IC-substituted TxRE binds CREB with increased affinity, suggesting flanking DNA influences the binding of CREB to the core CRE-like element. These data indicate that Tax does not regulate DNA binding of CREB by altering dimerization, but rather enhances DNA binding by additionally interacting with the minor groove of flanking DNA sequences.

Original languageEnglish (US)
Pages (from-to)19251-19259
Number of pages9
JournalJournal of Biological Chemistry
Volume273
Issue number30
DOIs
StatePublished - Jul 24 1998

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Deltaretrovirus
T-cells
Response Elements
Taxation
Viruses
Protein Binding
Carrier Proteins
DNA
DNA Footprinting
Terminal Repeat Sequences
Dimerization
Chromomycin A3
Protein Multimerization
GC Rich Sequence
Inosine
DNA-Binding Proteins
Guanine
Transcriptional Activation
DNA sequences
Fluorescence

ASJC Scopus subject areas

  • Biochemistry

Cite this

The human T-cell leukemia virus-1 transcriptional activator tax enhances cAMP-responsive element-binding protein (CREB) binding activity through interactions with the DNA minor groove. / Lundblad, James; Kwok, Roland P S; Laurance, Megan E.; Huang, Mary S.; Richards, Jane P.; Brennan, Richard G.; Goodman, Richard.

In: Journal of Biological Chemistry, Vol. 273, No. 30, 24.07.1998, p. 19251-19259.

Research output: Contribution to journalArticle

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