tailieunhanh - Báo cáo khoa học: Ribosomal protein L22 inhibits regulation of cellular activities by the Epstein-Barr virus small RNA EBER-1

Epstein–Barr virus (EBV) is a potent mitogenic and anti-apoptotic agent for B lymphocytes and is associated with several different types of human tumour. The abundantly expressed small viral RNA, EBER-1, binds to the growth inhibitory and pro-apoptotic protein kinase R (PKR) and blocks activation of the latter by double-stranded RNA. Recent evidence has suggested that expression of EBER-1 alone in EBV-negative B cells promotes a tumorigenic phe-notype and that this may be related to inhibition of the pro-apoptotic effects of PKR | Eur. J. Biochem. 271 1895-1905 2004 FEBS 2004 doi Ribosomal protein L22 inhibits regulation of cellular activities by the Epstein-Barr virus small RNA EBER-1 Androulla Elia Jashmin Vyas Kenneth G. Laingt and Michael J. Clemens Translational Control Group Department of Basic Medical Sciences St George s Hospital Medical School London UK Epstein-Barr virus EBV is a potent mitogenic and anti-apoptotic agent for B lymphocytes and is associated with several different types of human tumour. The abundantly expressed small viral RNA EBER-1 binds to the growth inhibitory and pro-apoptotic protein kinase R PKR and blocks activation of the latter by double-stranded RNA. Recent evidence has suggested that expression of EBER-1 alone in EBV-negative B cells promotes a tumorigenic phenotype and that this may be related to inhibition of the pro-apoptotic effects of PKR. The ribosomal protein L22 binds to EBER-1 in virus-infected cells but the significance of this has not previously been established. We report here that L22 and PKR compete for a common binding site on EBER-1. As a result of this competition L22 interferes with the ability of the small RNA to inhibit the activation of PKR by dsRNA. Transient expression of EBER-1 in murine embryonic fibroblasts stimulates reporter gene expression and partially reverses the inhibitory effect of PKR. However EBER-1 is also stimulatory when transfected into PKR knockout cells suggesting an additional PKR-independent mode of action of the small RNA. Expression of L22 prevents both the PKR-dependent and -independent effects of EBER-1 in vivo. These results suggest that the association of L22 with EBER-1 in EBV-infected cells can attenuate the biological effects of the viral RNA. Such effects include both the inhibition of PKR and additional mechanism s by which EBER-1 stimulates gene expression. Keywords double-stranded RNA EBV protein kinase R RNA-protein interactions translational control. Epstein-Barr .

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