Genomes and Genes
Gene Symbol: LMP-1
Description: latent membrane protein LMP-1;
Alias: latent membrane protein LMP-1;
Species: Epstein-Barr virus
- Cameron J, Yin Q, Fewell C, Lacey M, McBride J, Wang X, et al. Epstein-Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a, a modulator of lymphocyte signaling pathways. J Virol. 2008;82:1946-58 pubmed
- Ndour P, Ouk T, Brocqueville G, Mougel A, Vanhecke E, Feuillard J, et al. Inhibition of tumor necrosis factor-induced phenotypes by short intracellular versions of latent membrane protein-1. Cell Signal. 2010;22:303-13 pubmed publisher..These data demonstrate that LMP1 derived molecules can be used to design compounds with potential therapeutic roles in diseases due to TNF overactivation. ..
- Gatto G, Rossi A, Rossi D, Kroening S, Bonatti S, Mallardo M. Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kappaB pathway. Nucleic Acids Res. 2008;36:6608-19 pubmed publisher..Finally, we demonstrate that LMP1-mediated activation of miR-155 in an EBV-negative background correlates with reduction of protein PU.1, which is a possible miR target. ..
- Motsch N, Pfuhl T, Mrazek J, Barth S, Grässer F. Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) induces the expression of the cellular microRNA miR-146a. RNA Biol. 2007;4:131-7 pubmed..It is possible that the induction of miR-146a plays a role in the induction or maintenance of EBV latency by modulating innate immune responses to the virus infected host cell. ..
- Tsai C, Li H, Lu Y, Hsueh C, Liang Y, Chen C, et al. Activation of DNA methyltransferase 1 by EBV LMP1 Involves c-Jun NH(2)-terminal kinase signaling. Cancer Res. 2006;66:11668-76 pubmed..38%), suggesting that overexpression of these proteins is observed in NPC tumor. Overall, these results support a mechanistic link between JNK-AP-1 signaling and DNA methylation induced by the EBV oncogene product LMP1. ..
- Nagamine M, Takahara M, Kishibe K, Nagato T, Ishii H, Bandoh N, et al. Sequence variations of Epstein-Barr virus LMP1 gene in nasal NK/T-cell lymphoma. Virus Genes. 2007;34:47-54 pubmed
- Li L, Guo L, Tao Y, Zhou S, Wang Z, Luo W, et al. Latent membrane protein 1 of Epstein-Barr virus regulates p53 phosphorylation through MAP kinases. Cancer Lett. 2007;255:219-31 pubmed
- Soni V, Yasui T, Cahir McFarland E, Kieff E. LMP1 transmembrane domain 1 and 2 (TM1-2) FWLY mediates intermolecular interactions with TM3-6 to activate NF-kappaB. J Virol. 2006;80:10787-93 pubmed..These data support models in which the TM1 F38WLY41 effects are at least partially dependent on TM3 W98 and a residue(s) in TMs 5 and 6. ..
- Lo A, To K, Lo K, Lung R, Hui J, Liao G, et al. Modulation of LMP1 protein expression by EBV-encoded microRNAs. Proc Natl Acad Sci U S A. 2007;104:16164-9 pubmed..The data provide insight into the discrepancy between LMP1 transcript and protein detection in NPC and highlight the role of the EBV miRNAs in regulating LMP1 downstream signaling to promote cancer development. ..
- Shkoda A, Town J, Griese J, Romio M, Sarioglu H, Knöfel T, et al. The germinal center kinase TNIK is required for canonical NF-?B and JNK signaling in B-cells by the EBV oncoprotein LMP1 and the CD40 receptor. PLoS Biol. 2012;10:e1001376 pubmed publisher..Our data establish TNIK as a novel key player in TRAF6-dependent JNK and NF-?B signaling and a transducer of activating and transforming signals in human B-cells. ..
- Shair K, Bendt K, Edwards R, Nielsen J, Moore D, Raab Traub N. Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) and LMP2A function cooperatively to promote carcinoma development in a mouse carcinogenesis model. J Virol. 2012;86:5352-65 pubmed publisher..This study is the first to characterize the effects of LMP2 on tumor initiation and promotion and to identify an effect of the combined expression of LMP1 and LMP2 on the increase of carcinoma development. ..
- Boehm D, Gewurz B, Kieff E, Cahir McFarland E. Epstein-Barr latent membrane protein 1 transformation site 2 activates NF-kappaB in the absence of NF-kappaB essential modifier residues 133-224 or 373-419. Proc Natl Acad Sci U S A. 2010;107:18103-8 pubmed publisher..These data provide further evidence of the essential role for NEMO in LMP1 TES2 NF-?B activation and highlight the importance of unique domains within NEMO for sensing distinct NF-?B stimuli. ..
- Kondo S, Wakisaka N, Muramatsu M, Zen Y, Endo K, Murono S, et al. Epstein-Barr virus latent membrane protein 1 induces cancer stem/progenitor-like cells in nasopharyngeal epithelial cell lines. J Virol. 2011;85:11255-64 pubmed publisher..Our findings indicate that LMP1 can induce a CPC-like rather than a CSC-like phenotype in epithelial cells and suggest that LMP1-induced phenotypic changes contribute to the development of NPC. ..
- Brocqueville G, Ndour P, Ouk T, Le Goff A, De Witte C, Mougel A, et al. LMP1-induced cell death may contribute to the emergency of its oncogenic property. PLoS ONE. 2013;8:e60743 pubmed publisher..Our findings thus reconcile the apparent opposite apoptotic and oncogenic effects described for LMP1 and might reflect what actually happens on LMP1-induced cell transformation after EBV infection in patients. ..
- Chen J, Hu C, Hou J, Shao Q, Yan L, Zhu X, et al. Epstein-Barr virus encoded latent membrane protein 1 regulates mTOR signaling pathway genes which predict poor prognosis of nasopharyngeal carcinoma. J Transl Med. 2010;8:30 pubmed publisher..These results suggest that the mTOR signaling pathway is regulated by LMP1 expression in NPC. LMP1 and the genes in the mTOR pathway such as p-P70S6K and p-4EBP1 may be potential prognostic biomarkers. ..
- Khabir A, Karray H, Rodriguez S, Rose M, Daoud J, Frikha M, et al. EBV latent membrane protein 1 abundance correlates with patient age but not with metastatic behavior in north African nasopharyngeal carcinomas. Virol J. 2005;2:39 pubmed..The high amount of LMP1 recorded in tumors from young patients confirms that the juvenile form of NPC has specific features regarding not only cellular but also viral gene expression. ..
- Kung C, Meckes D, Raab Traub N. Epstein-Barr virus LMP1 activates EGFR, STAT3, and ERK through effects on PKCdelta. J Virol. 2011;85:4399-408 pubmed publisher..These findings indicate that LMP1 activates multiple distinct signaling pathways and suggest that PKC? functions as a master regulator of EGFR, STAT3, and ERK activation by LMP1-CTAR1. ..
- Endo K, Shackelford J, Aga M, Yoshizaki T, Pagano J. Upregulation of special AT-rich-binding protein 1 by Epstein-Barr virus latent membrane protein 1 in human nasopharyngeal cells and nasopharyngeal cancer. J Gen Virol. 2013;94:507-13 pubmed publisher..Taken together, our results suggest that SATB1 functions as a pro-metastatic effector of LMP1 signalling in EBV-positive NPC. ..
- Webb N, Connolly G, Tellam J, Yap A, Khanna R. Epstein-Barr virus associated modulation of Wnt pathway is not dependent on latent membrane protein-1. PLoS ONE. 2008;3:e3254 pubmed publisher..Taken together these studies demonstrate that EBV-mediated activation of Wnt pathway is not dependent on the expression of LMP1. ..
- Meckes D, Menaker N, Raab Traub N. Epstein-Barr virus LMP1 modulates lipid raft microdomains and the vimentin cytoskeleton for signal transduction and transformation. J Virol. 2013;87:1301-11 pubmed publisher..These findings indicate that LMP1 reorganizes membrane and cytoskeleton microdomains to modulate signal transduction. ..
- Ndour P, Brocqueville G, Ouk T, Goormachtigh G, Morales O, Mougel A, et al. Inhibition of latent membrane protein 1 impairs the growth and tumorigenesis of latency II Epstein-Barr virus-transformed T cells. J Virol. 2012;86:3934-43 pubmed publisher..Finally, we prove that synthetic peptides display similar inhibitory effects in EBV-infected cells. DNs derived from LMP1 could be used to develop therapeutic approaches for malignant diseases associated with EBV. ..
- Bentz G, Whitehurst C, Pagano J. Epstein-Barr virus latent membrane protein 1 (LMP1) C-terminal-activating region 3 contributes to LMP1-mediated cellular migration via its interaction with Ubc9. J Virol. 2011;85:10144-53 pubmed publisher..We propose that LMP1, by interaction with Ubc9, modulates sumoylation processes, which regulate signal transduction pathways that affect phenotypic changes associated with oncogenesis. ..
- Zhao Y, Wang Y, Zeng S, Hu X. LMP1 expression is positively associated with metastasis of nasopharyngeal carcinoma: evidence from a meta-analysis. J Clin Pathol. 2012;65:41-5 pubmed publisher..27 (95% CI 1.10 to 4.69) in the random-effects model. LMP1 expression is positively associated with metastasis in NPC, thus LMP1 detection in primary NPC might be an effective and feasible means to predict metastasis. ..
- Song Y, Kang M. Roles of TRAF2 and TRAF3 in Epstein-Barr virus latent membrane protein 1-induced alternative NF-kappaB activation. Virus Genes. 2010;41:174-80 pubmed publisher..Taken together, LMP1 activates alternative NF-kappaB pathway through functional NIK and IKKalpha that is regulated by TRAF2 or TRAF3. ..
- Liu H, Duan Z, Zheng H, Hu D, Li M, Tao Y, et al. EBV-encoded LMP1 upregulates Ig? 3'enhancer activity and Ig? expression in nasopharyngeal cancer cells by activating the Ets-1 through ERKs signaling. PLoS ONE. 2012;7:e32624 pubmed publisher..Our studies provide evidence for a novel regulatory mechanism of kappa expression, by which virus-encoded proteins activate the kappa 3' enhancer through activating transcription factors in non-B epithelial cancer cells. ..
- Uemura N, Kajino T, Sanjo H, Sato S, Akira S, Matsumoto K, et al. TAK1 is a component of the Epstein-Barr virus LMP1 complex and is essential for activation of JNK but not of NF-kappaB. J Biol Chem. 2006;281:7863-72 pubmed..These results suggest that an LMP1-associated complex containing TRAF6, TAB2, and TAK1 plays an essential role in the activation of JNK. However, TAK1 is not an exclusive intermediate for NF-kappaB activation in LMP1 signaling. ..
- Liu Y, Tan Y, Wang Z, Zeng L, Lu Z, Li L, et al. Phosphorylation and nuclear translocation of STAT3 regulated by the Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma. Int J Mol Med. 2008;21:153-62 pubmed
- Pratt Z, Zhang J, Sugden B. The latent membrane protein 1 (LMP1) oncogene of Epstein-Barr virus can simultaneously induce and inhibit apoptosis in B cells. J Virol. 2012;86:4380-93 pubmed publisher..These findings illustrate how the carboxy-terminal domain of LMP1 supports survival of B cells in the presence of the deleterious effects of the complex regulation of this viral oncogene. ..
- Liu H, Wu C, Chang Y. PRA1 promotes the intracellular trafficking and NF-kappaB signaling of EBV latent membrane protein 1. EMBO J. 2006;25:4120-30 pubmed..These novel findings provide important new insights into LMP1, and identify an unexpected new role for PRA1 in cellular signaling. ..
- Yu H, Lu J, Zuo L, Yan Q, Yu Z, Li X, et al. Epstein-Barr virus downregulates microRNA 203 through the oncoprotein latent membrane protein 1: a contribution to increased tumor incidence in epithelial cells. J Virol. 2012;86:3088-99 pubmed publisher..Inhibitors of Jun N-terminal protein kinase (JNK) and NF-?B blocked miR-203 downregulation. These results imply that EBV promotes malignancy by downregulating cellular miR-203, which contributes to the etiology of NPC. ..
- Liu H, Chen C, Wu C, Huang Y, Liu S, Liang Y, et al. Epstein-Barr virus-encoded LMP1 interacts with FGD4 to activate Cdc42 and thereby promote migration of nasopharyngeal carcinoma cells. PLoS Pathog. 2012;8:e1002690 pubmed publisher..Collectively, our results not only uncover a novel mechanism underlying LMP1-mediated Cdc42 activation, namely LMP1 interaction with FGD4, but also functionally link FGD4 to NPC tumorigenesis. ..
- Kanemitsu N, Isobe Y, Masuda A, Momose S, Higashi M, Tamaru J, et al. Expression of Epstein-Barr virus-encoded proteins in extranodal NK/T-cell Lymphoma, nasal type (ENKL): differences in biologic and clinical behaviors of LMP1-positive and -negative ENKL. Clin Cancer Res. 2012;18:2164-72 pubmed publisher..3% and 12.5%, respectively (P = 0.001, log-rank test). LMP1 expression shows correlations with phosphorylation of RelA and Akt and possibly has a favorable impact on clinical outcome in ENKL. ..
- Li J, Zhang X, Xie D, Deng H, Gao Y, Chen Q, et al. Expression of immune-related molecules in primary EBV-positive Chinese nasopharyngeal carcinoma: associated with latent membrane protein 1 (LMP1) expression. Cancer Biol Ther. 2007;6:1997-2004 pubmed..It has been reported that the expression pattern of immune related-molecules on tumor cells will affect the outcome of T-cell-based adoptive immunotherapy for NPC. ..
- Morris M, Dawson C, Wei W, O Neil J, Stewart S, Jia J, et al. Epstein-Barr virus-encoded LMP1 induces a hyperproliferative and inflammatory gene expression programme in cultured keratinocytes. J Gen Virol. 2008;89:2806-20 pubmed publisher..Identification of these LMP1-regulated genes helps to define the mechanism(s) by which this oncoprotein influences cellular pathways that regulate terminal differentiation, cell motility and inflammation. ..
- Gewurz B, Mar J, Padi M, Zhao B, Shinners N, Takasaki K, et al. Canonical NF-kappaB activation is essential for Epstein-Barr virus latent membrane protein 1 TES2/CTAR2 gene regulation. J Virol. 2011;85:6764-73 pubmed publisher..001-fold and >2-fold changes. Thus, canonical NF-?B activation is critical for almost all LMP1 TES2 RNA effects in HEK-293 cells and a more significant therapeutic target than previously appreciated. ..
- Verweij F, van Eijndhoven M, Hopmans E, Vendrig T, Wurdinger T, Cahir McFarland E, et al. LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-?B activation. EMBO J. 2011;30:2115-29 pubmed publisher..CD63 is thus a critical mediator of LMP1 function in- and outside-infected (tumour) cells. ..
- Vaysberg M, Hatton O, Lambert S, Snow A, Wong B, Krams S, et al. Tumor-derived variants of Epstein-Barr virus latent membrane protein 1 induce sustained Erk activation and c-Fos. J Biol Chem. 2008;283:36573-85 pubmed publisher..Our results indicate that the enhanced ability of tumor-derived LMP1 to induce and stabilize the c-Fos oncogene can be localized to two amino acids in the C terminus of LMP1. ..
- Song Y, Jen K, Soni V, Kieff E, Cahir McFarland E. IL-1 receptor-associated kinase 1 is critical for latent membrane protein 1-induced p65/RelA serine 536 phosphorylation and NF-kappaB activation. Proc Natl Acad Sci U S A. 2006;103:2689-94 pubmed..Thus, the critical IRAK1 role in LMP1-induced NF-kappaB activation is in mediating p65/RelA S536 phosphorylation through an effect on p38 or other p65 S536 kinases. ..
- Thornburg N, Raab Traub N. Induction of epidermal growth factor receptor expression by Epstein-Barr virus latent membrane protein 1 C-terminal-activating region 1 is mediated by NF-kappaB p50 homodimer/Bcl-3 complexes. J Virol. 2007;81:12954-61 pubmed..The distinct forms of NF-kappaB that are induced by LMP1 CTAR1 likely activate distinct cellular genes. ..
- Arcipowski K, Bishop G. TRAF binding is required for a distinct subset of in vivo B cell functions of the oncoprotein LMP1. J Immunol. 2012;189:5165-70 pubmed publisher..These data suggest that TRAF-mediated signaling pathways, such as those of LMP1, may be more diverse than previously appreciated. This finding has significant implications for receptor and TRAF-targeted therapies. ..
- Kutz H, Reisbach G, Schultheiss U, Kieser A. The c-Jun N-terminal kinase pathway is critical for cell transformation by the latent membrane protein 1 of Epstein-Barr virus. Virology. 2008;371:246-56 pubmed..Our data support a critical role of the LMP1-induced JNK pathway for proliferation of LMP1-transformed cells and characterize JNK as a potential target for intervention against EBV-induced malignancies...
- Dawson C, Port R, Young L. The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC). Semin Cancer Biol. 2012;22:144-53 pubmed publisher..Here we review the effects of LMP1 and LMP2 on various aspects of epithelial cell behaviour highlighting key aspects that may contribute to the pathogenesis of NPC. ..
- Wu Z, Chow K, Kuo T, Chang Y, Chao C. Latent membrane protein 1 of Epstein-Barr virus sensitizes cancer cells to cisplatin by enhancing NF-?B p50 homodimer formation and downregulating NAPA expression. Biochem Pharmacol. 2011;82:1860-72 pubmed publisher..These findings provide an explanatory mechanism for the pro-apoptotic activity of LMP1 as well as new therapeutic targets to control tumor growth. ..
- Chang P, Wu Z, Sun N, Chao C. EBV-encoded LMP-1 sensitizes nasopharyngeal carcinoma cells to genotoxic drugs by down-regulating Cabin1 expression. J Cell Physiol. 2014;229:309-22 pubmed publisher..This study reveals the molecular mechanism underlying the pro-apoptotic activity of LMP1 during cisplatin-based NPC chemotherapy. ..
- Renzette N, Somasundaran M, Brewster F, Coderre J, Weiss E, McManus M, et al. Epstein-Barr virus latent membrane protein 1 genetic variability in peripheral blood B cells and oropharyngeal fluids. J Virol. 2014;88:3744-55 pubmed publisher..The significance of EBV genetic diversity in transmission and disease pathogenesis are discussed. ..
- Zhang Q, Zhang Z, Wang C, Xiao Z, Yu Y, Yang F, et al. Proteome analysis of the transformation potential of the Epstein-Barr virus-encoded latent membrane protein 1 in nasopharyngeal epithelial cells NP69. Mol Cell Biochem. 2008;314:73-83 pubmed publisher..These data are valuable for further study of the mechanism of LMP1 in human nasopharyngeal carcinoma and provide some new clues for investigating other LMP1-associated tumors. ..
- Xu G, Wang H, He G, Xie K. [Expression and significance of p53-related proteins and LMP-1 in nasal NK/T-cell lymphoma]. Zhonghua Zhong Liu Za Zhi. 2009;31:351-5 pubmed..The expression of p53 protein is an independent prognostic factor. Though no significant relationship was found between the expression of LMP-1 protein and the clinical stage or prognosis, it may play some role in tumor progression. ..
- Zuo L, Yu H, Liu L, Tang Y, Wu H, Yang J, et al. The copy number of Epstein-Barr virus latent genome correlates with the oncogenicity by the activation level of LMP1 and NF-ÎºB. Oncotarget. 2015;6:41033-44 pubmed publisher..Overall, both the presence and amount of EBV genome are crucial for the viral oncogenicity. ..
- Rosales Perez S, Cano Valdez A, Flores Balcázar C, Guedea Edo F, Lino Silva L, Lozano Borbalas A, et al. Expression of Epstein-Barr virus-encoded latent membrane protein (LMP-1), p16 and p53 proteins in nonendemic nasopharyngeal carcinoma (NPC): a clinicopathological study. Arch Med Res. 2014;45:229-36 pubmed publisher..Probably, LMP1 and p16 detection identify a worse clinical prognosis in NPC patient subgroup. ..
- Hong S, Kim S, Jin D, Kim Y, Hur D. RPS27a enhances EBV-encoded LMP1-mediated proliferation and invasion by stabilizing of LMP1. Biochem Biophys Res Commun. 2017;491:303-309 pubmed publisher..These results suggest that RSP27a could be a potential target in EBV-infected LMP1-positive cancer cells. ..
- Lin S, Lee D, Law A, Fang J, Chua D, Lau A. A role for protein kinase PKR in the mediation of Epstein-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression. Cytokine. 2010;50:210-9 pubmed publisher..Our findings thus suggest that PKR plays an important role in mediating the cytokine gene expression induced by LMP1 through NF-kappaB activation and histone H3 Ser 10 phosphorylation. ..
- Shin D, Kim A, Kang H, Park S, Kim D, Lee S. Histone deacetylase inhibitor romidepsin induces efficient tumor cell lysis via selective down-regulation of LMP1 and c-myc expression in EBV-positive diffuse large B-cell lymphoma. Cancer Lett. 2015;364:89-97 pubmed publisher..In conclusion, romidepsin exerts strong anti-tumor activity in EBV-positive DLBCL via the inhibition of both LMP1 and c-myc. Our findings indicate that romidepsin might be a promising treatment for EBV-positive DLBCL. ..
- Chew M, Gan S, Khoo A, Tan E. Interleukins, laminin and Epstein - Barr virus latent membrane protein 1 (EBV LMP1) promote metastatic phenotype in nasopharyngeal carcinoma. BMC Cancer. 2010;10:574 pubmed publisher..These findings implicate the roles of EBV LMP1, laminin and IL-6 in the promotion of invasion and metastasis in NPC...
- Wang X, Saludes J, Zhao T, Csakai A, Fiorini Z, Chavez S, et al. Targeting the lateral interactions of transmembrane domain 5 of Epstein-Barr virus latent membrane protein 1. Biochim Biophys Acta. 2012;1818:2282-9 pubmed publisher..These studies demonstrated a new strategy for identifying small molecule disruptors for investigating transmembrane protein-protein interactions...
- You S, Han A, Zhang F, Song Y, Liang Y, Dong Y. [Effect of Epstein-Barr virus-encoded latent membrane protein 1 on ?-catenin transcriptional activity and expression in nasopharyngeal carcinoma]. Zhonghua Bing Li Xue Za Zhi. 2010;39:537-41 pubmed..4) LMP1 expression did not affect the total protein expression level of ?-catenin in both CNE1 and CNE2 cell lines. EB virus-encoded LMP1 may be involved in the pathogenesis of NPC via ?-catenin signal pathway. ..
- Sides M, Klingsberg R, Shan B, Gordon K, Nguyen H, Lin Z, et al. The Epstein-Barr virus latent membrane protein 1 and transforming growth factor--?1 synergistically induce epithelial--mesenchymal transition in lung epithelial cells. Am J Respir Cell Mol Biol. 2011;44:852-62 pubmed publisher..Our in vitro data may help to explain the observation that patients with IPF demonstrating positive staining for LMP1 in lung epithelial cells have a more rapid demise than patients in whom LMP1 is not detected...