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- Publisher Website: 10.1038/sj.onc.1206407
- Scopus: eid_2-s2.0-0037780825
- PMID: 12776188
- WOS: WOS:000183128500003
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Article: Kaposi's sarcoma-associated herpesvirus encoded vFLIP induces cellular IL-6 expression: The role of the NF-κB and JNK/AP1 pathways
Title | Kaposi's sarcoma-associated herpesvirus encoded vFLIP induces cellular IL-6 expression: The role of the NF-κB and JNK/AP1 pathways |
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Authors | |
Keywords | vFLIP NF-κB KSHV AP1 Interleukin-6 Jun N-terminal kinase |
Issue Date | 2003 |
Citation | Oncogene, 2003, v. 22, n. 22, p. 3371-3385 How to Cite? |
Abstract | The Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a FADD-like interferon converting enzyme or caspase 8 (FLICE) inhibitory protein (vFLIP) that prevents death receptor-mediated apoptosis by inhibiting the recruitment and activation of FLICE. Since vFLIP physically interacts with tumor necrosis factor receptor associated factor 2 (TRAF2) and TRAF2 mediates activation of the jun NH2-terminal kinase (JNK)/activation protein 1 (AP1) pathway, we hypothesized that vFLIP might also activate this pathway. To evaluate this hypothesis, we transiently and stably transfected a vFLIP expression construct and performed several complementary assays to document that vFLIP activates the JNK/AP1 pathway and does so in a TRAF-dependent fashion. As vFLIP also activates the nuclear factor κB (NF-κB) signaling pathway and the NF-κB and JNK/AP1 pathways both modulate cellular interleukin-6 (cIL-6) expression, we postulated that vFLIP induces expression of this cytokine. We show that vFLIP induces cIL-6 expression and activates the cIL-6 promoter, and maximal activation of the cIL-6 promoter by vFLIP requires NF-κB and AP1 activation. In addition, vFLIP and latency-associated nuclear antigen (LANA), another KSHV-encoded latent protein, potentiate each other's ability to activate the cIL-6 promoter. Gene silencing experiments by RNA interference demonstrate that vFLIP in BCBL-1 endogenously infected primary effusion lymphoma (PEL) cells mediates JNK/AP1 activation and cIL-6 expression. Thus, we conclude that vFLIP, in addition to its known effects on NF-κB activation, also modulates the JNK/AP1 pathway and induces gene expression from the cIL-6 promoter in a JNK/AP1-dependent fashion. |
Persistent Identifier | http://hdl.handle.net/10722/285576 |
ISSN | 2023 Impact Factor: 6.9 2023 SCImago Journal Rankings: 2.334 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | An, Jiabin | - |
dc.contributor.author | Sun, Yiping | - |
dc.contributor.author | Sun, Ren | - |
dc.contributor.author | Rettig, Matthew B. | - |
dc.date.accessioned | 2020-08-18T04:56:06Z | - |
dc.date.available | 2020-08-18T04:56:06Z | - |
dc.date.issued | 2003 | - |
dc.identifier.citation | Oncogene, 2003, v. 22, n. 22, p. 3371-3385 | - |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.uri | http://hdl.handle.net/10722/285576 | - |
dc.description.abstract | The Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a FADD-like interferon converting enzyme or caspase 8 (FLICE) inhibitory protein (vFLIP) that prevents death receptor-mediated apoptosis by inhibiting the recruitment and activation of FLICE. Since vFLIP physically interacts with tumor necrosis factor receptor associated factor 2 (TRAF2) and TRAF2 mediates activation of the jun NH2-terminal kinase (JNK)/activation protein 1 (AP1) pathway, we hypothesized that vFLIP might also activate this pathway. To evaluate this hypothesis, we transiently and stably transfected a vFLIP expression construct and performed several complementary assays to document that vFLIP activates the JNK/AP1 pathway and does so in a TRAF-dependent fashion. As vFLIP also activates the nuclear factor κB (NF-κB) signaling pathway and the NF-κB and JNK/AP1 pathways both modulate cellular interleukin-6 (cIL-6) expression, we postulated that vFLIP induces expression of this cytokine. We show that vFLIP induces cIL-6 expression and activates the cIL-6 promoter, and maximal activation of the cIL-6 promoter by vFLIP requires NF-κB and AP1 activation. In addition, vFLIP and latency-associated nuclear antigen (LANA), another KSHV-encoded latent protein, potentiate each other's ability to activate the cIL-6 promoter. Gene silencing experiments by RNA interference demonstrate that vFLIP in BCBL-1 endogenously infected primary effusion lymphoma (PEL) cells mediates JNK/AP1 activation and cIL-6 expression. Thus, we conclude that vFLIP, in addition to its known effects on NF-κB activation, also modulates the JNK/AP1 pathway and induces gene expression from the cIL-6 promoter in a JNK/AP1-dependent fashion. | - |
dc.language | eng | - |
dc.relation.ispartof | Oncogene | - |
dc.subject | vFLIP | - |
dc.subject | NF-κB | - |
dc.subject | KSHV | - |
dc.subject | AP1 | - |
dc.subject | Interleukin-6 | - |
dc.subject | Jun N-terminal kinase | - |
dc.title | Kaposi's sarcoma-associated herpesvirus encoded vFLIP induces cellular IL-6 expression: The role of the NF-κB and JNK/AP1 pathways | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1038/sj.onc.1206407 | - |
dc.identifier.pmid | 12776188 | - |
dc.identifier.scopus | eid_2-s2.0-0037780825 | - |
dc.identifier.volume | 22 | - |
dc.identifier.issue | 22 | - |
dc.identifier.spage | 3371 | - |
dc.identifier.epage | 3385 | - |
dc.identifier.isi | WOS:000183128500003 | - |
dc.identifier.issnl | 0950-9232 | - |