LMP-2A

Summary

Gene Symbol: LMP-2A
Description: membrane protein LMP-2A;
Alias: membrane protein LMP-2A;
Species: Epstein-Barr virus

Top Publications

  1. Lung R, Tong J, Sung Y, Leung P, Ng D, Chau S, et al. Modulation of LMP2A expression by a newly identified Epstein-Barr virus-encoded microRNA miR-BART22. Neoplasia. 2009;11:1174-84 pubmed
    ..Our findings emphasize the role of miR-BART22 in modulating LMP2A expression, which may facilitate NPC carcinogenesis by evading the host immune response...
  2. Bultema R, Longnecker R, Swanson Mungerson M. Epstein-Barr virus LMP2A accelerates MYC-induced lymphomagenesis. Oncogene. 2009;28:1471-6 pubmed publisher
    ..These results support a hypothesis that EBV LMP2A promotes tumor development by protecting pre-tumor B cells that would normally apoptose after the c-myc translocation. ..
  3. Kong Q, Hu L, Cao J, Huang Y, Xu L, Liang Y, et al. Epstein-Barr virus-encoded LMP2A induces an epithelial-mesenchymal transition and increases the number of side population stem-like cancer cells in nasopharyngeal carcinoma. PLoS Pathog. 2010;6:e1000940 pubmed publisher
    ..Taken together, our data indicate that LMP2A induces EMT and stem-like cell self-renewal in NPC, suggesting a novel mechanism by which Epstein-Barr virus induces the initiation, metastasis and recurrence of NPC...
  4. Rovedo M, Longnecker R. Epstein-barr virus latent membrane protein 2B (LMP2B) modulates LMP2A activity. J Virol. 2007;81:84-94 pubmed
    ..A restoration of Lyn levels, but not a change in LMP2A levels, was also observed in cells coexpressing LMP2B with LMP2A. From these results, we conclude that LMP2B modulates LMP2A activity. ..
  5. Mancao C, Hammerschmidt W. Epstein-Barr virus latent membrane protein 2A is a B-cell receptor mimic and essential for B-cell survival. Blood. 2007;110:3715-21 pubmed
  6. Wang H, Nicholas M, Conway K, Sen P, Diz R, Tisch R, et al. EBV latent membrane protein 2A induces autoreactive B cell activation and TLR hypersensitivity. J Immunol. 2006;177:2793-802 pubmed
    ..These data further implicate TLRs in the etiology of SLE and suggest a mechanistic link between EBV infection and SLE. ..
  7. Hino R, Uozaki H, Inoue Y, Shintani Y, Ushiku T, Sakatani T, et al. Survival advantage of EBV-associated gastric carcinoma: survivin up-regulation by viral latent membrane protein 2A. Cancer Res. 2008;68:1427-35 pubmed publisher
  8. Fukuda M, Longnecker R. Epstein-Barr virus latent membrane protein 2A mediates transformation through constitutive activation of the Ras/PI3-K/Akt Pathway. J Virol. 2007;81:9299-306 pubmed
    ..These results suggest that constitutive activation of the Ras/PI3-K/Akt pathway by LMP2A is a key factor for LMP2A-mediated transformation. ..
  9. Anderson L, Longnecker R. An auto-regulatory loop for EBV LMP2A involves activation of Notch. Virology. 2008;371:257-66 pubmed
    ..The observation that LMP2A activates its own promoter suggests that LMP2A exploits the Notch pathway in order to control its own expression and may explain EBNA2-independent expression of LMP2A in EBV-associated malignancies. ..

More Information

Publications40

  1. Matskova L, Helmstetter C, Ingham R, Gish G, Lindholm C, Ernberg I, et al. The Shb signalling scaffold binds to and regulates constitutive signals from the Epstein-Barr virus LMP2A membrane protein. Oncogene. 2007;26:4908-17 pubmed publisher
    ..Our data set the precedent for viral utilization of the Shb signalling scaffold and implicate Shb as a regulator of LMP2A-dependent Akt activation...
  2. Anderson L, Longnecker R. EBV LMP2A provides a surrogate pre-B cell receptor signal through constitutive activation of the ERK/MAPK pathway. J Gen Virol. 2008;89:1563-8 pubmed publisher
    ..Constitutive phosphorylation of ERK/MAPK and PI3K/Akt in TgE LMP2A bone marrow B cells is also reminiscent of signalling through the pre-BCR, altogether demonstrating that LMP2A provides a pre-BCR-like signal to developing B cells...
  3. Incrocci R, McCormack M, Swanson Mungerson M. Epstein-Barr virus LMP2A increases IL-10 production in mitogen-stimulated primary B-cells and B-cell lymphomas. J Gen Virol. 2013;94:1127-33 pubmed publisher
    ..These data identify a novel function of LMP2A in the alteration of a cytokine that is important for both tumour survival and anti-tumour responses...
  4. Chang R, Miller S, Longnecker R. Epstein-Barr virus latent membrane protein 2A exacerbates experimental autoimmune encephalomyelitis and enhances antigen presentation function. Sci Rep. 2012;2:353 pubmed publisher
    ..This difference was not due to lymphocyte recruitment into the CNS or differences in T cell activation, rather, we show that LMP2A enhances antigen presentation function. ..
  5. Hsiao F, Tai A, Deglon A, Sutkowski N, Longnecker R, Huber B. EBV LMP-2A employs a novel mechanism to transactivate the HERV-K18 superantigen through its ITAM. Virology. 2009;385:261-6 pubmed publisher
    ..After truncating 25 kb of genomic sequence downstream of HERV-K18, LMP-2A failed to transactivate HERV-K18 env. Thus, an LMP-2A-inducible element is located downstream of HERV-K18...
  6. Bieging K, Amick A, Longnecker R. Epstein-Barr virus LMP2A bypasses p53 inactivation in a MYC model of lymphomagenesis. Proc Natl Acad Sci U S A. 2009;106:17945-50 pubmed publisher
    ..This work shows that LMP2A can permit tumorigenesis in the presence of an intact p53 pathway, identifying an important contribution of EBV to BL...
  7. Zhu S, Xue X, Liu J, Lu L, Zhao P, Wang J, et al. Expression of HPV6b L1/EBV LMP2 multiepitope and immunogenicity in mice. Acta Biochim Biophys Sin (Shanghai). 2010;42:515-21 pubmed publisher
    ..The present results confirmed that HPV L1 protein is potential to deliver multiepitope of EBV LMP2 as immunogen to the MHC class I and class II pathways, extending the use of HPV L1 as delivery vehicles. ..
  8. Wirtz T, Weber T, Kracker S, Sommermann T, Rajewsky K, Yasuda T. Mouse model for acute Epstein-Barr virus infection. Proc Natl Acad Sci U S A. 2016;113:13821-13826 pubmed
    ..Thus, timed expression of LMP1 together with LMP2A in subsets of mouse B cells allows one to study major clinically relevant features of human EBV infection in vivo, opening the way to new therapeutic approaches. ..
  9. Iwakiri D, Minamitani T, Samanta M. Epstein-Barr virus latent membrane protein 2A contributes to anoikis resistance through ERK activation. J Virol. 2013;87:8227-34 pubmed publisher
    ..These findings suggest that LMP2A-mediated ERK activation is involved in the generation of EBV-associated epithelial malignancies...
  10. 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. ..
  11. Pan Y, Vatsyayan J, Chang Y, Chang H. Epstein-Barr virus latent membrane protein 2A upregulates UDP-glucose dehydrogenase gene expression via ERK and PI3K/Akt pathway. Cell Microbiol. 2008;10:2447-60 pubmed publisher
    ..This study provides a model for molecular mechanism participating in LMP2A-mediated UGDH gene activation...
  12. Xu J, Yao K, Yu C, Chen X, Li B, Sun H, et al. [Expression and significance of EBV LMP2A in nasopharyngeal cancer specimens]. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2005;19:484-7 pubmed
    ..There is a possibility of applying LMP2A target antigen to induce specific immunoreaction to kill tumor cells of NPC. ..
  13. Anderson L, Longnecker R. Epstein-Barr virus latent membrane protein 2A exploits Notch1 to alter B-cell identity in vivo. Blood. 2009;113:108-16 pubmed publisher
    ..Interestingly, Notch1 appears to be important for LMP2A-mediated survival in low interleukin-7. We propose that LMP2A and the Notch1 pathway may cooperate to induce the alterations in B-cell identity seen in Hodgkin Reed-Sternberg cells...
  14. Ikeda M, Longnecker R. The c-Cbl proto-oncoprotein downregulates EBV LMP2A signaling. Virology. 2009;385:183-91 pubmed publisher
    ..Combine with these new findings, we propose a model in which c-Cbl and Nedd4-family E3s cooperate to degrade target proteins at discrete steps in the function of the LMP2A signalosome...
  15. Han J, Chen J, Zhang Z, Li H, Ding Y, Du H, et al. Sequence variations of latent membrane protein 2A in Epstein-Barr virus-associated gastric carcinomas from Guangzhou, southern China. PLoS ONE. 2012;7:e34276 pubmed publisher
    ..This, to our best knowledge, is the first detailed investigation of LMP2A polymorphisms in EBVaGC in Guangzhou, southern China, where NPC is endemic. ..
  16. Dergai O, Dergai M, Skrypkina I, Matskova L, Tsyba L, Gudkova D, et al. The LMP2A protein of Epstein-Barr virus regulates phosphorylation of ITSN1 and Shb adaptors by tyrosine kinases. Cell Signal. 2013;25:33-40 pubmed publisher
    ..Considering that Shb and ITSN1 are implicated in various receptor tyrosine kinase signaling, our results indicate that LMP2A can affect a number of signaling pathways by regulating the phosphorylation of the ITSN1 and Shb adaptors...
  17. Shore A, White P, Hui R, Essafi A, Lam E, Rowe M, et al. Epstein-Barr virus represses the FoxO1 transcription factor through latent membrane protein 1 and latent membrane protein 2A. J Virol. 2006;80:11191-9 pubmed publisher
    ..Expression of the EBV genes for latent membrane protein 1 and latent membrane protein 2A decreases FoxO1 expression. Thus, our data elucidate distinct mechanisms for the regulation of the proapoptotic transcription factor FoxO1 by EBV...
  18. Ikeda M, Longnecker R. Cholesterol is critical for Epstein-Barr virus latent membrane protein 2A trafficking and protein stability. Virology. 2007;360:461-8 pubmed publisher
    ..LMP2A in the exosomal fraction was ubiquitinated but not phosphorylated. These results indicate that cholesterol-dependent LMP2A trafficking determines the fate of LMP2A degradation...
  19. Nagamine M, Kishibe K, Takahara M, Nagato T, Ishii H, Bandoh N, et al. Selected amino acid change encoding Epstein-Barr virus-specific T cell epitope of the LMP2A gene in Japanese nasal NK/T cell lymphoma patients. Intervirology. 2007;50:319-22 pubmed
    ..The LMP2A strain including threonine substitution at codon 348 may be selected within tumors and play a role for tumor genesis in Japanese patients with nasal NK/T cell lymphoma through reduced immune recognition. ..
  20. Fotheringham J, Coalson N, Raab Traub N. Epstein-Barr virus latent membrane protein-2A induces ITAM/Syk- and Akt-dependent epithelial migration through ?v-integrin membrane translocation. J Virol. 2012;86:10308-20 pubmed publisher
    ..The specific effects of LMP2A on an integrin with a diverse repertoire of ligand specificities could promote migration of different cell types and be initiated by multiple chemoattractants. ..
  21. Minamitani T, Ma Y, Zhou H, Kida H, Tsai C, Obana M, et al. Mouse model of Epstein-Barr virus LMP1- and LMP2A-driven germinal center B-cell lymphoproliferative disease. Proc Natl Acad Sci U S A. 2017;114:4751-4756 pubmed publisher
    ..Collectively, our results highlight synergistic EBV membrane oncoprotein effects on GC B cells and provide a model for studies of their roles in immunosuppression-related lymphoproliferative diseases. ..
  22. Gross H, Hennard C, Masouris I, Cassel C, Barth S, Stober Gr sser U, et al. Binding of the heterogeneous ribonucleoprotein K (hnRNP K) to the Epstein-Barr virus nuclear antigen 2 (EBNA2) enhances viral LMP2A expression. PLoS ONE. 2012;7:e42106 pubmed publisher
    ..Our data support the notion that the methylated surface of EBNA2 mimics the surface structure of cellular proteins to interfere with or co-opt their functional properties...
  23. Du Z, Hu L, Wang H, Yan L, Zeng Y, Shao J, et al. Upregulation of MiR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A and downregulates a negative prognostic marker JMJD1A. PLoS ONE. 2011;6:e19137 pubmed publisher
    ..The potential of miR-155 and JMJD1A as therapeutic targets in NPC should be further investigated...
  24. Mao Y, Zhang D, Zhu H, Lin H, Xiong L, Cao Q, et al. LMP1 and LMP2A are potential prognostic markers of extranodal NK/T-cell lymphoma, nasal type (ENKTL). Diagn Pathol. 2012;7:178 pubmed publisher
    ..049, p = 0.036). LMP1 and LMP2A may be prognostic indicators of survival in patients with ENKTL. http://www.diagnosticpathology.diagnomx.eu/vs/2443352538545899...
  25. Vockerodt M, Wei W, Nagy E, Prouzova Z, Schrader A, Kube D, et al. Suppression of the LMP2A target gene, EGR-1, protects Hodgkin's lymphoma cells from entry to the EBV lytic cycle. J Pathol. 2013;230:399-409 pubmed publisher
    ..The primary microarray data are available from GEO (http://www.ncbi.nlm.nih.gov/geo/) under series Accession No 46143...
  26. Lan Y, Hsiao J, Chang K, Chang J, Chen C, Lai H, et al. Epstein-Barr virus latent membrane protein 2A promotes invasion of nasopharyngeal carcinoma cells through ERK/Fra-1-mediated induction of matrix metalloproteinase 9. J Virol. 2012;86:6656-67 pubmed publisher
  27. Wasil L, Tomaszewski M, Hoji A, Rowe D. The effect of Epstein-Barr virus Latent Membrane Protein 2 expression on the kinetics of early B cell infection. PLoS ONE. 2013;8:e54010 pubmed publisher
    ..In contrast, LMP2B did not appear to play a significant role in these processes, and long-term growth of infected B cells was not affected by the absence of this protein. ..
  28. Gerle B, Koroknai A, Fejer G, Bakos A, Banati F, Szenthe K, et al. Acetylated histone H3 and H4 mark the upregulated LMP2A promoter of Epstein-Barr virus in lymphoid cells. J Virol. 2007;81:13242-7 pubmed publisher
    ..Our results suggest that the combinatorial effects of DNA methylation, histone acetylation, and H3K4me2 modulate the activity of LMP2Ap...
  29. Swanson Mungerson M, Bultema R, Longnecker R. Epstein-Barr virus LMP2A imposes sensitivity to apoptosis. J Gen Virol. 2010;91:2197-202 pubmed publisher
    ..These data suggest that LMP2A uniquely makes resting B-cells sensitive to NF-kappaB inhibition and apoptosis and suggest that NF-kappaB may be a novel target to eradicate latently EBV-infected B-cells...
  30. Rechsteiner M, Bernasconi M, Berger C, Nadal D. Role of latent membrane protein 2 isoforms in Epstein-Barr virus latency. Trends Microbiol. 2008;16:520-7 pubmed publisher
    ..Based on recent insights in the function of LMP2B, an isoform of LMP2A, we propose a model for how LMP2B modulates the activity of LMP2A contributing to maintenance of EBV latency...
  31. 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. ..