Kaposi's sarcoma-associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 suppresses CXCR4 expression by upregulating miR-146a.
Kaposi's sarcoma-associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 suppresses CXCR4 expression by upregulating miR-146a.
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DOI：
10.1038/onc.2009.460
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发表时间：
2010-03-25
期刊：
影响因子：
8
通讯作者：
Chaudhary PM
中科院分区：
文献类型：
--
作者：
Punj V;Matta H;Schamus S;Tamewitz A;Anyang B;Chaudhary PM
Kaposi's sarcoma (KS) associated herpesvirus (KSHV)-encoded viral FLICE inhibitory protein (vFLIP) K13 is a potent activator of the NF-κB pathway. Here we demonstrate that infection with KHSV and ectopic expression of K13, but not its NF-κB-defective mutant, suppressed the expression of CXCR4. Suppression of CXCR4 by KSHV and K13 was associated with upregulated expression of miR-146a, a microRNA that is known to bind to the 3′ untranslated region of CXCR4 mRNA. Reporter studies identified two NF-κB sites in the promoter of miR-146a that were essential for its activation by K13. Accordingly, ectopic expression of K13, but not its NF-κB-defective mutant or other vFLIPs, strongly stimulated the miR-146a promoter activity, which could be blocked by specific genetic and pharmacological inhibitors of the NF-κB pathway. Finally, expression of CXCR4 was downregulated in clinical samples of KS and this was accompanied by increased expression of miR-146a. Our results demonstrate that K13-induced NF-κB activity suppresses CXCR4 via upregulation of miR-146a. Downregulation of CXCR4 expression by K13 may contribute to KS development by promoting premature release of KSHV-infected endothelial progenitors into the circulation.
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DOI：
10.1084/jem.20031467
发表时间：
2004-04-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guasparri I;Keller SA;Cesarman E
通讯作者：
Cesarman E
影响因子：
5.4
作者：
Cameron, Jennifer E.;Yin, Qinyan;Flemington, Erik K.
通讯作者：
Flemington, Erik K.
影响因子：
8
作者：
Matta, H.;Punj, V.;Chaudhary, P. M.
通讯作者：
Chaudhary, P. M.
影响因子：
5.4
作者：
Moses, AV;Fish, KN;Nelson, JA
通讯作者：
Nelson, JA
影响因子：
4.8
作者：
Matta, Hittu;Mazzacurati, Lucia;Chaudhary, Preet M.
通讯作者：
Chaudhary, Preet M.