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Epstein-Barr virus-encoded LMP1 promotes cisplatin-induced caspase activation through JNK and NF-kappaB signaling pathways.
Biochem Biophys Res Commun. 2007 Aug 17; 360(1):263-8.BB

Abstract

Our previous studies have shown that Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) potentiates chemotherapeutic agent-induced apoptosis in human cell lines of epithelial origin: cervical carcinoma-derived HeLa cells and nasopharyngeal carcinoma-derived TW03 cells. LMP1 acted upstream of caspase-dependent mitochondrial perturbation, and the effect was mapped to the C-terminal signaling domain of LMP1, designated CTAR2. CTAR2 is known to engage the c-Jun N-terminal kinase (JNK) and NF-kappaB pathways, and we show here that SP600125, a selective JNK inhibitor, suppresses LMP1 potentiation of cisplatin-induced mitochondrial damage and caspase activation in HeLa cells. Moreover, the potentiation of cisplatin-triggered caspase activation was blocked by Bay11-7082, a potent inhibitor of NF-kappaB. Similar results were obtained when a dominant negative form of IkappaB, a specific repressor of NF-kappaB, was co-expressed with LMP1. The current data support the notion that LMP1 modifies stress-induced apoptosis in epithelial cells through molecular interactions downstream of its C-terminal signaling domain.

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Authors+Show Affiliations

Zhang X
Department of Microbiology, Tumor and Cell Biology, Box 280, Karolinska Institutet, 171 77 Stockholm, Sweden.
Sanmun D
No affiliation info available
Hu L
No affiliation info available
Fadeel B
No affiliation info available
Ernberg I
No affiliation info available

MeSH

CaspasesCisplatinEnzyme ActivationHeLa CellsHumansMAP Kinase Kinase 4NF-kappa BSignal TransductionViral Matrix Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17586463

Citation

Zhang, Xiangning, et al. "Epstein-Barr Virus-encoded LMP1 Promotes Cisplatin-induced Caspase Activation Through JNK and NF-kappaB Signaling Pathways." Biochemical and Biophysical Research Communications, vol. 360, no. 1, 2007, pp. 263-8.
Zhang X, Sanmun D, Hu L, et al. Epstein-Barr virus-encoded LMP1 promotes cisplatin-induced caspase activation through JNK and NF-kappaB signaling pathways. Biochem Biophys Res Commun. 2007;360(1):263-8.
Zhang, X., Sanmun, D., Hu, L., Fadeel, B., & Ernberg, I. (2007). Epstein-Barr virus-encoded LMP1 promotes cisplatin-induced caspase activation through JNK and NF-kappaB signaling pathways. Biochemical and Biophysical Research Communications, 360(1), 263-8.
Zhang X, et al. Epstein-Barr Virus-encoded LMP1 Promotes Cisplatin-induced Caspase Activation Through JNK and NF-kappaB Signaling Pathways. Biochem Biophys Res Commun. 2007 Aug 17;360(1):263-8. PubMed PMID: 17586463.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epstein-Barr virus-encoded LMP1 promotes cisplatin-induced caspase activation through JNK and NF-kappaB signaling pathways. AU - Zhang,Xiangning, AU - Sanmun,Duangmanee, AU - Hu,LiFu, AU - Fadeel,Bengt, AU - Ernberg,Ingemar, Y1 - 2007/06/18/ PY - 2007/06/01/received PY - 2007/06/08/accepted PY - 2007/6/26/pubmed PY - 2007/9/6/medline PY - 2007/6/26/entrez SP - 263 EP - 8 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 360 IS - 1 N2 - Our previous studies have shown that Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) potentiates chemotherapeutic agent-induced apoptosis in human cell lines of epithelial origin: cervical carcinoma-derived HeLa cells and nasopharyngeal carcinoma-derived TW03 cells. LMP1 acted upstream of caspase-dependent mitochondrial perturbation, and the effect was mapped to the C-terminal signaling domain of LMP1, designated CTAR2. CTAR2 is known to engage the c-Jun N-terminal kinase (JNK) and NF-kappaB pathways, and we show here that SP600125, a selective JNK inhibitor, suppresses LMP1 potentiation of cisplatin-induced mitochondrial damage and caspase activation in HeLa cells. Moreover, the potentiation of cisplatin-triggered caspase activation was blocked by Bay11-7082, a potent inhibitor of NF-kappaB. Similar results were obtained when a dominant negative form of IkappaB, a specific repressor of NF-kappaB, was co-expressed with LMP1. The current data support the notion that LMP1 modifies stress-induced apoptosis in epithelial cells through molecular interactions downstream of its C-terminal signaling domain. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/17586463/Epstein_Barr_virus_encoded_LMP1_promotes_cisplatin_induced_caspase_activation_through_JNK_and_NF_kappaB_signaling_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(07)01284-3 DB - PRIME DP - Unbound Medicine ER -