The 2 Faces of JNK Signaling in Cancer

Tournier, Cathy

doi:10.1177/1947601913486349

Cited by 142 publications

(126 citation statements)

References 52 publications

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“…MAPKs regulate a number of cellular functions, such as gene expression, cell differentiation, proliferation, and death. JNK is important for cell stress responses, cellular apoptosis pathways, and inflammatory responses (52,53). Two EBV immediate early proteins, BZLF1 and BRFL1, and two latent proteins, LMP1 and LMP2, have previously been shown to activate JNK (9,17,22), and BZLF1, BRLF1, and LMP1 have also been reported to activate p38 (22,37).…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus (EBV) Tegument Protein BGLF2 Promotes EBV Reactivation through Activation of the p38 Mitogen-Activated Protein Kinase

Liu

Cohen

2016

J Virol

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IMPORTANCE Epstein-Barr virus (EBV) is associated with both B cell and epithelial cell malignancies, and the virus activates multiple signaling pathways important for its persistence in latently infected cells. We identified a viral tegument protein, BGLF2, which activates members of the mitogen-activated protein kinase signaling pathway. Expression of BGLF2 increased expression of EBV BZLF1, which activates a switch from latent to lytic virus infection, and increased production of EBV. Inhibition of BGFL2 expression or inhibition of p38/MAPK, which is activated by BGLF2, reduced virus reactivation from latency. These results indicate that a viral tegument protein which is delivered to cells upon infection activates signaling pathways to enhance virus production and facilitate virus reactivation from latency. E pstein-Barr virus (EBV) is a cause of infectious mononucleosis and is associated with both B lymphocyte and epithelial cell malignancies. EBV encodes a number of proteins that trigger cell signaling pathways, such as AP-1, JAK-STAT, NF-B, and phosphatidylinositol 3-kinase (PI3K)/Akt, which are critical for cell survival, virus latency, and growth transformation (1-6). For example, EBV latent membrane protein 1 (LMP1) mimics CD40 signaling and is important for EBV-induced B cell growth proliferation, inhibition of apoptosis, and EBV transformation. LMP1 interacts with tumor necrosis factor receptor-associated factors (TRAFs), leading to activation of NF-B, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), PI3K/Akt, and STAT3 (7-12). EBV LMP2A mimics B cell receptor signaling and contributes to the long-term survival of B cells (13-16). LMP2A activates extracellular signal-related protein kinase (ERK), PI3K/Akt, and JNK (17) and downregulates NF-B and STAT signaling pathways (18). The EBV immediate early protein BZLF1 activates virus reactivation from latency (19-21). BZLF1 activates p38 and JNK to turn on the ATF2 transcription factor (22). BRLF1, another EBV immediate early protein, activates the AP-1 pathway by increasing the levels of phosphorylated p38, JNK, and ERK (22, 23) and induces phosphorylation of Akt through the PI3K pathway (24). Activation of Akt, ERK, and p38 signaling is required for EBV reactivation from latency (25-28).To identify additional EBV proteins important for regulating cell signaling, we used a proteomic approach to screen viral proteins for AP-1 promoter activity in AP-1-luciferase reporter assays. We found that the EBV tegument protein BGLF2 induced AP-1 reporter activity and activated p38 and JNK. BGLF2 promoted EBV reactivation by enhancing BZLF1 expression and EBV production, and p38 activation by BGLF2 was required for these activities. Citation Liu X, Cohen JI. 2016. Epstein-Barr virus (EBV) tegument protein BGLF2 promotes EBV reactivation through activation of the p38 mitogen-activated protein kinase.

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Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus (EBV) Tegument Protein BGLF2 Promotes EBV Reactivation through Activation of the p38 Mitogen-Activated Protein Kinase

Liu

Cohen

2016

J Virol

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“…Previous studies have revealed the conflicting roles of JNK, depending on tumor type (12). JNK pathway inactivation decreases tumor growth in gastric or intestinal tumors (13,14), indicating its pro-tumorigenic role.…”

Section: Introductionmentioning

confidence: 99%

JNK pathway inhibition enhances chemotherapeutic sensitivity to Adriamycin in nasopharyngeal carcinoma cells

et al. 2017

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“…The functions of JNKs and p38 MAPK in the modulation of cell proliferation and apoptosis are presently being explored for the development of targeted therapies. [25][26][27] Several mouse models have shown that p38 MAPK signaling suppresses the formation of breast, lung and liver tumors in vivo. 28) Furthermore, mice deficient in Gadd45a, a JNK and p38 MAPK pathways activator, exhibited the promotion of Ras-induced breast tumorigenesis and decreased apoptosis.…”

Section: Discussionmentioning

confidence: 99%

A Novel Peptide from <i>Vespa ducalis</i> Induces Apoptosis in Osteosarcoma Cells by Activating the p38 MAPK and JNK Signaling Pathways

Tang

et al. 2018

Biological & Pharmaceutical Bulletin

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The 2 Faces of JNK Signaling in Cancer

Cited by 142 publications

References 52 publications

Epstein-Barr Virus (EBV) Tegument Protein BGLF2 Promotes EBV Reactivation through Activation of the p38 Mitogen-Activated Protein Kinase

Epstein-Barr Virus (EBV) Tegument Protein BGLF2 Promotes EBV Reactivation through Activation of the p38 Mitogen-Activated Protein Kinase

JNK pathway inhibition enhances chemotherapeutic sensitivity to Adriamycin in nasopharyngeal carcinoma cells

A Novel Peptide from <i>Vespa ducalis</i> Induces Apoptosis in Osteosarcoma Cells by Activating the p38 MAPK and JNK Signaling Pathways

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