Evidence that protein kinase A activity is required for the basal and tax-stimulated transcriptional activity of human T-cell leukemia virus type- I long terminal repeat

Hava Turgeman, Mordechai Aboud

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The present study was undertaken to investigate the role of protein kinase A (PKA) in the control of human T-cell leukemia virus type-I (HTLV-I) long terminal repeat (LTR) expression, since this issue is still controversial. For this purpose we employed two human T-cell lines; the Jurkat cells in which long exposure to diBu-cAMP severely down-regulated the catalytic subunit of PKA (PKA-C), and H-9 cells in which such exposure markedly increased PKA-C level. Transient transfection assays revealed that addition of diBu-cAMP 1 h before or after transfection profoundly increased HTLV-I LTR directed CAT expression and synergistically enhanced its stimulation by the viral transactivator tax gene product in both cell lines. However longer exposure to diBu-cAMP before transfection reduced LTR-CAT expression to below its basal level and completely abolished its stimulation by tax in Jurkat cells, and this diBu-cAMP inhibitory effect could be abrogated by cotransfection of a PKA-C expressing vector. By contrast, in H- 9 cells, this long exposure to diBu-cAMP continued enhancing LTR-CAT expression and its tax-mediated transactivation, and this stimulatory effect of diBu-cAMP could be diminished by the PKA-specific inhibitor N-12-(p- bromocinnamylamine)ethyl]-5-isoquinolinsulfonamide (H-89). Notably, in the absence of diBu-cAMP treatment H-89 reduced LTR-CAT expression to below its basal level and prevented its stimulation by tax in both cell lines. Together these findings indicate not only that cAMP-activated PKA stimulates HTLV-I LTR expression and its transactivation by tax, but even in the absence of PKA activating signals the basal HTLV-I LTR expression as well as its stimulation by tax are both dependent on a basal PKA activity.

Original languageEnglish
Pages (from-to)183-187
Number of pages5
JournalFEBS Letters
Volume428
Issue number3
DOIs
StatePublished - 29 May 1998

Keywords

  • Dibutyryl-cAMP
  • H-89
  • HTLV-I
  • LTR-CAT
  • Protein kinase A (PKA)
  • Tax

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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