Latent membrane protein 1 of Epstein–Barr virus sensitizes cancer cells to cisplatin by enhancing NF-κB p50 homodimer formation and downregulating NAPA expression

Wu, Zchong-Zcho; Chow, Kai-Ping N.; Kuo, Tsung-Cheng; Chang, Yu‐Sun; Chao, Chuck C.‐K.

doi:10.1016/j.bcp.2011.09.010

Cited by 13 publications

(8 citation statements)

References 44 publications

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“…4A). Similar amounts of NF-B p50 subunit were detected both before and after TNF-␣ stimulation, which we think is consistent with previous observations that low levels of the p50 subunit are present on specific NF-B-responsive promoters in the nucleus of unstimulated cells as the p50 homodimer, whereas the majority of this subunit is retained in the cytoplasm as RelA/p50 (33)(34)(35). The p50 homodimer itself does not contain transactivation domains, but it associates with promoter regions of some NF-B-dependent genes, including integrated HIV-1 LTR in the unstimulated conditions (36).…”

Section: Kinetics Of Rela Recruitment Upon Tnf-␣ Stimulation Correlatsupporting

confidence: 92%

Double Plant Homeodomain (PHD) Finger Proteins DPF3a and -3b Are Required as Transcriptional Co-activators in SWI/SNF Complex-dependent Activation of NF-κB RelA/p50 Heterodimer

Ishizaka

Mizutani

Kobayashi

et al. 2012

Journal of Biological Chemistry

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Background:The NF-B dimer, RelA/p50, often requires the SWI/SNF complex for its transactivation function, but its molecular mechanisms remain elusive. Results: The NF-B canonical pathway induced by TNF-␣ is DPF3a/b-and SWI/SNF-dependent for some promoters. Conclusion: DPF3a and DPF3b are effective linkers for the SWI/SNF complex and RelA/p50. Significance: The NF-B⅐DPF3a/b⅐SWI/SNF complex would be an effective platform for promoter-specific transactivation.

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Section: Kinetics Of Rela Recruitment Upon Tnf-␣ Stimulation Correlatsupporting

confidence: 92%

Double Plant Homeodomain (PHD) Finger Proteins DPF3a and -3b Are Required as Transcriptional Co-activators in SWI/SNF Complex-dependent Activation of NF-κB RelA/p50 Heterodimer

Ishizaka

Mizutani

Kobayashi

et al. 2012

Journal of Biological Chemistry

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“…Further experiments are needed to examine whether additional ERK-regulated transcription factors may regulate Cabin1 gene expression. Similar observations were reported for the NF-kB-dependent transcriptional regulation of the Napa gene by LMP1 knockdown in mouse Balb/c-3T3 cells (Wu et al, 2011a).…”

Section: Discussionsupporting

confidence: 88%

“…4), suggesting that LMP1 negatively regulates Cabin1 gene expression by downregulating kinase pathways. Similar observations were reported for the NF-kB-dependent transcriptional regulation of the Napa gene by LMP1 knockdown in mouse Balb/c-3T3 cells (Wu et al, 2011a). However, the same assays did not show enhanced binding of Elk-1, a target of the ERK pathway (Besnard et al, 2011).…”

Section: Discussionsupporting

confidence: 84%

EBV‐Encoded LMP‐1 Sensitizes Nasopharyngeal Carcinoma Cells to Genotoxic Drugs by Down‐Regulating Cabin1 Expression

Chang

Sun

et al. 2013

Journal Cellular Physiology

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The oncogenic latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is involved in the pathogenesis of human nasopharyngeal carcinoma (NPC) and lymphoma. We and other authors have shown earlier that LMP1 induces apoptosis and inhibits xenograft tumor growth in mice, but the mechanism underlying these processes has not been investigated so far. In the present study, we show that knockdown of LMP1 renders the EBV-positive NPC cell line CG-1 resistant to various genotoxic drugs (cisplatin, etoposide, and adriamycin). LMP1 inhibits the expression of Cabin1, a Ca(2+) regulated protein shown earlier to inhibit calcineurin. Knockdown of calcineurin binding protein (Cabin1) with small hairpin RNA sensitizes CG-1 cells to genotoxic drugs. In contrast, LMP1 overexpression reduces Cabin1 level and renders both CG-1 cells and EBV-negative NPC cell lines sensitive to cisplatin. The c-Jun-N-terminal kinase (JNK) and ERK pathways are required for LMP1-induced suppression of Cabin1 at the transcriptional level. Chromatin immunoprecipitation assays further confirm that the JNK-activated transcription factor AP-1 mediates the LMP1-induced down-regulation of Cabin1 gene expression. LMP1 knockdown also increases the resistance of xenograph tumors to cisplatin in mice, therefore confirming the relevance of our findings in vivo. This study reveals the molecular mechanism underlying the pro-apoptotic activity of LMP1 during cisplatin-based NPC chemotherapy.

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“…Furthermore, loss of ␣SNAP expression was detected in the brain of Down syndrome fetuses (86) and in the striatum of patients with Huntington disease (87). Finally, some viral proteins reportedly down-regulate ␣SNAP levels in tumor cells, thereby sensitizing these cells to death-inducing stimuli (41). This data demonstrates an intriguing possibility that the ␣SNAP level can serve as a molecular rheostat determining cellular responses and behavior in different pathological conditions.…”

Section: Discussionmentioning

confidence: 82%

N-Ethylmaleimide-sensitive Factor Attachment Protein α (αSNAP) Regulates Matrix Adhesion and Integrin Processing in Human Epithelial Cells

Naydenov

Feygin

Wang

et al. 2014

Journal of Biological Chemistry

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Background: Vesicle trafficking plays important roles in regulating cell adhesion and motility. Results: Depletion of the membrane fusion protein, N-ethylmaleimide-sensitive factor attachment protein ␣ (␣SNAP), induced cell detachment, whereas overexpression of this vesicle regulator increased cell-matrix adhesion. Conclusion: ␣SNAP promotes cell-matrix adhesion by controlling integrin trafficking and assembly of focal adhesions. Significance: The ␣SNAP level may serve as a molecular rheostat controlling matrix adhesion and cell motility under normal conditions and in diseases.

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Latent membrane protein 1 of Epstein–Barr virus sensitizes cancer cells to cisplatin by enhancing NF-κB p50 homodimer formation and downregulating NAPA expression

Cited by 13 publications

References 44 publications

Double Plant Homeodomain (PHD) Finger Proteins DPF3a and -3b Are Required as Transcriptional Co-activators in SWI/SNF Complex-dependent Activation of NF-κB RelA/p50 Heterodimer

Double Plant Homeodomain (PHD) Finger Proteins DPF3a and -3b Are Required as Transcriptional Co-activators in SWI/SNF Complex-dependent Activation of NF-κB RelA/p50 Heterodimer

EBV‐Encoded LMP‐1 Sensitizes Nasopharyngeal Carcinoma Cells to Genotoxic Drugs by Down‐Regulating Cabin1 Expression

N-Ethylmaleimide-sensitive Factor Attachment Protein α (αSNAP) Regulates Matrix Adhesion and Integrin Processing in Human Epithelial Cells

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