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

FEBS Letters

Aboud, Mordechai¹  Turgeman, Hava¹ 

[1] Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel

关键词: HTLV-I;    tax;    LTR-CAT;    Protein kinase A (PKA);    Dibutyryl-cAMP;    H-89;   

DOI  :  10.1016/S0014-5793(98)00513-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 co-transfection 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-[2-(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.

【 授权许可】

Unknown