LMP1 of Epstein–Barr virus suppresses cellular senescence associated with the inhibition of p16INK4a expression
Abstract
Epstein-Barr virus is associated with a number of human proliferative and malignant diseases. It is capable of immortalizing human primary B-lymphocytes in vitro. Studies indicate that latent membrane protein LMP1 is one of the viral proteins essential for this process. In this report, LMP1 was shown to prevent primary mouse embryonic fibroblasts from entering into replicative senescence in vitro. It further suppresses the senescence-associated induction of p16INK4a, commonly believed to be a key regulator of replicative senescence. In addition, LMP1 was shown to prevent premature senescence provoked by oncogenic ras in mouse embryonic fibroblasts, and to inhibit the oncogene ras-mediated induction of p16INK4a and p21WAF1. In parallel, LMP1 also prevents ras-induced premature senescence in rat embryonic fibroblasts REF52 and human diploid fibroblasts IMR90. Moreover, LMP1 is capable of suppressing the p16INK4a promoter in REF52 and Saos-2 cells in a promoter reporter assay. Our findings suggest that with the expression of p16INK4a and replicative senescence being suppressed, LMP1 may play a key role in Epstein-Barr virus-associated proliferative diseases, and it may further contribute to cancer development by preventing premature senescence induced by mitogenic oncogenes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
EBV infection induces expression of p16INK4a or p21CIP1, which act as a primary host defence against virus propagation, and EBV-positive cells losing expression of these mediators are selected for in manifest chronic infection.
“EBV infection has long been known to induce the expression of central signalling mediators of the senescence response such as p16INK4a or p21CIP1. These proteins act as a primary host defence against virus propagation, and EBV-positive cells losing expression of these mediators subsequently get selected for in manifest chronic infection187,188.”
From COVID-19 and cellular senescence (2023) · cites this paper as [187]
Cites
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508 · see citing works
WAF1, a potential mediator of p53 tumor suppression
El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W., & Vogelstein, B. (1993) · Cell · doi:10.1016/0092-8674(93)90500-p · Cited by 8,321 · see citing works
p53, the cellular gatekeeper for growth and division
Levine, A. J. (1997) · Cell · doi:10.1016/s0092-8674(00)81871-1 · Cited by 7,693 · see citing works
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477 · see citing works
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,178 · cited 10× · see citing works
“LMP1 overcomes the premature senescence provoked by exogenous H-Ras61L in MEF cells Previous studies have revealed that ras oncogene induces premature senescence associated with the induction of p16 and p53 (Serrano et al., 1997).”
BackgroundMethodResultInfluentialVIRUS PARTICLES IN CULTURED LYMPHOBLASTS FROM BURKITT'S LYMPHOMA
Epstein, M. A., Achong, B. G., & Barr, Y. M. (1964) · The Lancet · doi:10.1016/s0140-6736(64)91524-7 · Cited by 2,793 · see citing works
Epstein-Barr virus and its replication
Kieff, E. D. (1996) · Medical Entomology and Zoology · Cited by 1,627 · see citing works
Role of the INK4a Locus in Tumor Suppression and Cell Mortality
Serrano, M., Lee, H.-W., Chin, L., Cordon-Cardo, C., Beach, D., & DePinho, R. A. (1996) · Cell · doi:10.1016/s0092-8674(00)81079-x · Cited by 1,585 · see citing works
An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells
Wang, D., Liebowitz, D. N., & Kieff, E. D. (1985) · Cell · doi:10.1016/0092-8674(85)90256-9 · Cited by 1,253 · see citing works
Alcorta, D. A., Xiong, Y., Phelps, D., Hannon, G., Beach, D., & Barrett, J. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13742 · Cited by 1,008 · see citing works
Mosialos, G., Birkenbacht, M., Yalamanchill, R., Arsdale, T. V., Ware, C. F., & Kleff, E. (1995) · Cell · doi:10.1016/0092-8674(95)90489-1 · Cited by 980 · see citing works
Lin, A. W., Barradas, M., Stone, J. C., van Aelst, L., Serrano, M., & Lowe, S. W. (1998) · Genes & Development · doi:10.1101/gad.12.19.3008 · Cited by 945 · see citing works
The structure of the termini of the Epstein-Barr virus as a marker of clonal cellular proliferation
Raab‐Traub, N., & Flynn, K. (1986) · Cell · doi:10.1016/0092-8674(86)90803-2 · Cited by 926 · see citing works
Stein, G. H., Drullinger, L. F., Soulard, A., & Dulić, V. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.3.2109 · Cited by 868 · see citing works
Senescence of human fibroblasts induced by oncogenic Raf
Zhu, J., Woods, D., McMahon, M., & Bishop, J. M. (1998) · Genes & Development · doi:10.1101/gad.12.19.2997 · Cited by 826 · see citing works
Brown, J. P., Wei, W., & Sedivy, J. M. (1997) · Science · doi:10.1126/science.277.5327.831 · Cited by 804 · see citing works
Greenspan, J. S., Greenspan, D., Lennette, E. T., Abrams, D. I., Conant, M. A., Petersen, V., & Freese, U. K. (1985) · New England Journal of Medicine · doi:10.1056/nejm198512193132502 · Cited by 797 · see citing works
Epstein-Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation.
Kaye, K. M., Izumi, K. M., & Kieff, E. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.19.9150 · Cited by 777 · see citing works
Hara, E., Smith, R., Parry, D., Tahara, H., Stone, S., & Peters, G. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.3.859 · Cited by 733 · see citing works
Replicative Senescence: the Human Fibroblast Comes of Age
Goldstein, S. (1990) · Science · doi:10.1126/science.2204114 · Cited by 651 · see citing works
Rajadurai, P., Prasad, U., Sadler, R. H., Flynn, K., & Raab‐Traub, N. (1995) · New England Journal of Medicine · doi:10.1056/nejm199509143331103 · Cited by 618 · see citing works
Zindy, F., Quelle, D. E., Roussel, M. F., & Sherr, C. J. (1997) · Oncogene · doi:10.1038/sj.onc.1201178 · Cited by 574 · see citing works
Genetic analysis of immortalizing functions of Epstein–Barr virus in human B lymphocytes
Hammerschmidt, W., & Sugden, B. (1989) · Nature · doi:10.1038/340393a0 · Cited by 552 · see citing works
X-LINKED RECESSIVE PROGRESSIVE COMBINED VARIABLE IMMUNODEFICIENCY (DUNCAN'S DISEASE)
Purtilo, D., Yang, J. S., Cassel, C., Harper, R., Stephenson, S., Landing, B. H., & Vawter, G. (1975) · The Lancet · doi:10.1016/s0140-6736(75)92004-8 · Cited by 551 · see citing works
The biology of replicative senescence
Campisi, J. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(96)00058-5 · Cited by 538 · see citing works
Epstein-Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation.
Cohen, J. I., Wang, F., Mannick, J. B., & Kieff, E. D. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.23.9558 · Cited by 483 · see citing works
Kilger, E., Kieser, A., Baumann, M., & Hammerschmidt, W. (1998) · The EMBO Journal · doi:10.1093/emboj/17.6.1700 · Cited by 482 · see citing works
Myc and Ras collaborate in inducing accumulation of active cyclin E/Cdk2 and E2F
Leone, G. W., DeGregori, J. V., Sears, R. C., Jakoi, L., & Nevins, J. R. (1997) · Nature · doi:10.1038/387422a0 · Cited by 468 · see citing works
The Pathogenesis of Burkitt's Lymphoma
MAGRATH, I. T. (1990) · Advances in cancer research · doi:10.1016/s0065-230x(08)60470-4 · Cited by 461 · see citing works
Latent membrane protein 1 of Epstein–Barr virus mimics a constitutively active receptor molecule
Gires, O., Zimber‐Strobl, U., Gonnella, R., Ueffing, M., Marschall, G., Zeidler, R., Pich, D., & Hammerschmidt, W. (1997) · The EMBO Journal · doi:10.1093/emboj/16.20.6131 · Cited by 451 · see citing works
Replicative Senescence: An Old Lives' Tale?
Campisi, J. (1996) · Cell · doi:10.1016/s0092-8674(00)81023-5 · Cited by 434 · see citing works
Izumi, K. M., & Kieff, E. D. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.23.12592 · Cited by 394 · see citing works
Tomkinson, B. E., Robertson, E. S., & Kieff, E. (1993) · Journal of Virology · doi:10.1128/jvi.67.4.2014-2025.1993 · Cited by 391 · see citing works
Independent binding of the retinoblastoma protein and p107 to the transcription factor E2F
Cao, L., Faha, B., Dembski, M., Tsai, L., Harlow, E., & Dyson, N. J. (1992) · Nature · doi:10.1038/355176a0 · Cited by 357 · see citing works
Self-citationLatent membrane protein 1 of Epstein–Barr virus interacts with JAK3 and activates STAT proteins
Gires, O., Kohlhuber, F., Kilger, E., Baumann, M., Kieser, A., Kaiser, C., Zeidler, R., Scheffer, B., Ueffing, M., & Hammerschmidt, W. (1999) · The EMBO Journal · doi:10.1093/emboj/18.11.3064 · Cited by 349 · see citing works
The INK4 family of cell cycle inhibitors in cancer
Roussel, M. F. (1999) · Oncogene · doi:10.1038/sj.onc.1202998 · Cited by 323 · see citing works
Kieser, A., Kilger, E., Gires, O., Ueffing, M., Kölch, W., & Hammerschmidt, W. (1997) · The EMBO Journal · doi:10.1093/emboj/16.21.6478 · Cited by 319 · see citing works
McConnell, B. B., Starborg, M., Brookes, S., & Peters, G. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70137-x · Cited by 314 · see citing works
Presence of EB Virus Nucleic Acid Homology in a “Virus-free” Line of Burkitt Tumour Cells
Hausen, H. Z., & Schulte‐Holthausen, H. (1970) · Nature · doi:10.1038/227245a0 · Cited by 311 · see citing works
Mitchell, T. L., & Sugden, B. (1995) · Journal of Virology · doi:10.1128/jvi.69.5.2968-2976.1995 · Cited by 271 · see citing works
Suzuki, T., Kitao, S., Matsushime, H., & Yoshida, M. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00505.x · Cited by 269 · see citing works
Eliopoulos, A. G., & Young, L. S. (1998) · Oncogene · doi:10.1038/sj.onc.1201694 · Cited by 269 · see citing works
Mannick, J. B., Cohen, J. I., Birkenbach, M. P., Marchini, A., & Kieff, E. D. (1991) · Journal of Virology · doi:10.1128/jvi.65.12.6826-6837.1991 · Cited by 236 · see citing works
Izumi, K. M., Kaye, K. M., & Kieff, E. D. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.4.1447 · Cited by 223 · see citing works
Draetta, G. F. (1994) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(94)90054-x · Cited by 220 · see citing works
Dominant inhibitory mutations in the Mg(2+)-binding site of RasH prevent its activation by GTP.
Farnsworth, C. L., & Feig, L. A. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.10.4822 · Cited by 211 · see citing works
Pantoja, C., & Serrano, M. (1999) · Oncogene · doi:10.1038/sj.onc.1202880 · Cited by 201 · cited 2× · see citing works
“Mutation in p16 or p53, but not p21, abolishes oncogene ras induced premature senescence of MEF cells (Serrano et al., 1997; Pantoja and Serrano, 1999).”
BackgroundDetection of Epstein-Barr virus genomes in Hodgkin's disease: relation to age.
Jarrett, R. F., Gallagher, A., Jones, D. B., Alexander, F. E., Krajewski, A. S., Kelsey, A. M., Adams, J., Angus, B., Gledhill, S., & Wright, D. H. (1991) · Journal of Clinical Pathology · doi:10.1136/jcp.44.10.844 · Cited by 187 · see citing works
Moorthy, R. K., & Thorley‐Lawson, D. A. (1993) · Journal of Virology · doi:10.1128/jvi.67.3.1638-1646.1993 · Cited by 176 · see citing works
Kaye, K. M., Izumi, K. M., Mosialos, G., & Kieff, E. D. (1995) · Journal of Virology · doi:10.1128/jvi.69.2.675-683.1995 · Cited by 172 · see citing works
Franza, B. R., Maruyama, K., Garrels, J. I., & Ruley, H. E. (1986) · Cell · doi:10.1016/0092-8674(86)90462-9 · Cited by 166 · see citing works
Increased p53 Protein Associated with Aging in Human Diploid Fibroblasts
Kulju, K. S., & Lehman, J. M. (1995) · Experimental Cell Research · doi:10.1006/excr.1995.1095 · Cited by 155 · cited 1× · see citing works
“The increased expressions of p53, p21, and p16 are detected in human cells which have undergone senescence (Kulju and Lehman, 1995; Alcorta et al., 1996).”
BackgroundHammerschmidt, W., Sugden, B., & Baichwal, V. R. (1989) · Journal of Virology · doi:10.1128/jvi.63.6.2469-2475.1989 · Cited by 151 · see citing works
An infrequent point mutation of the p53 gene in human nasopharyngeal carcinoma.
Sun, Y., Hegamyer, G. A., Cheng, Y. J., Hildesheim, A., Chen, J. Y., Chen, I.-H., Cao, Y., Yao, K., & Colburn, N. H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.14.6516 · Cited by 143 · see citing works
Origins of G<sub>1</sub> arrest in senescent human fibroblasts
Stein, G. H., & Dulić, V. (1995) · BioEssays · doi:10.1002/bies.950170610 · Cited by 135 · see citing works
Induction of senescence in human malignant glioma cells by p16INK4A
Uhrbom, L., Nistér, M., & Westermark, B. (1997) · Oncogene · doi:10.1038/sj.onc.1201227 · Cited by 133 · see citing works
Human T-cell leukemia virus type 1 Tax releases cell cycle arrest induced by p16INK4a
Low, K. G., Dorner, L. F., Fernando, D. B., Grossman, J., Jeang, K. T., & Comb, M. J. (1997) · Journal of Virology · doi:10.1128/jvi.71.3.1956-1962.1997 · Cited by 132 · see citing works
Absence of p53 allows direct immortalization of hematopoietic cells by the myc and raf oncogenes
Metz, T. M., Harris, A. W., & Adams, J. M. (1995) · Cell · doi:10.1016/0092-8674(95)90049-7 · Cited by 122 · see citing works
Dominant Inhibitory Mutations in the Mg2+-Binding Site of RasH Prevent Its Activation by GTP
Farnsworth, C. L., & Feig, L. A. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.10.4822-4829.1991 · Cited by 83 · see citing works
Kaye, K. M., Izumi, K. M., Li, H., Johannsen, E., Davidson, D., Longnecker, R., & Kieff, E. D. (1999) · Journal of Virology · doi:10.1128/jvi.73.12.10525-10530.1999 · Cited by 82 · see citing works
Interactions between Ras proteins and their effectors
McCormick, F. P., & Wittinghofer, A. (1996) · Current Opinion in Biotechnology · doi:10.1016/s0958-1669(96)80123-6 · Cited by 80 · see citing works
Yang, X., Sham, J. S. T., Ng, M. H., Tsao, S., Zhang, D., Lowe, S. W., & Cao, L. (2000) · Journal of Virology · doi:10.1128/jvi.74.2.883-891.2000 · Cited by 38 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Regulation of the INK4b–ARF–INK4a tumour suppressor locus: all for one or one for all
Gil, J., & Peters, G. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1987 · Cited by 843 · see citing works
PML is induced by oncogenic <i>ras</i> and promotes premature senescence
Ferbeyre, G., de Stanchina, E., Querido, E., Baptiste, N., Prives, C., & Lowe, S. W. (2000) · Genes & Development · doi:10.1101/gad.14.16.2015 · Cited by 536 · see citing works
p16(MTS-1/CDKN2/INK4a) in Cancer Progression
Rocco, J. W., & Sidransky, D. (2001) · Experimental Cell Research · doi:10.1006/excr.2000.5149 · Cited by 464 · see citing works
Dawson, W. O., Port, R. J., & Young, L. S. (2012) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2012.01.004 · Cited by 356 · see citing works
Regulatory Mechanisms of Tumor Suppressor P16INK4Aand Their Relevance to Cancer
Li, J., Poi, M. J., & Tsai, M. (2011) · Biochemistry · doi:10.1021/bi200642e · Cited by 336 · see citing works
Id proteins in cell cycle control and cellular senescence
Zebedee, Z., & Hara, E. (2001) · Oncogene · doi:10.1038/sj.onc.1205092 · Cited by 277 · see citing works
Ohtani, N., Yamakoshi, K., Takahashi, A., & Hara, E. (2004) · The Journal of Medical Investigation · doi:10.2152/jmi.51.146 · Cited by 276 · see citing works
LMP1 structure and signal transduction
Eliopoulos, A. G., & Young, L. S. (2001) · Seminars in Cancer Biology · doi:10.1006/scbi.2001.0410 · Cited by 236 · see citing works
The significance of LMP1 expression in nasopharyngeal carcinoma
Tsao, S. W., Tramoutanis, G., Dawson, W. O., Lo, A. K. F., & Huang, D. P. (2002) · Seminars in Cancer Biology · doi:10.1016/s1044579x02000901 · Cited by 204 · see citing works
Chen, H., Hutt‐Fletcher, L. M., Cao, L., & Hayward, S. D. (2003) · Journal of Virology · doi:10.1128/jvi.77.7.4139-4148.2003 · Cited by 166 · see citing works
Self-citationCOVID-19 and cellular senescence
Schmitt, C. A., Tchkonia, T., Niedernhofer, L. J., Robbins, P. D., Kirkland, J. L., & Lee, S. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-022-00785-2 · Cited by 153 · see citing works
Molecular virology of Epstein–Barr virus
Bornkamm, G. W., & Hammerschmidt, W. (2001) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2000.0781 · Cited by 146 · see citing works
Skalska, L., White, R. E., Franz, M., Ruhmann, M., & Allday, M. J. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000951 · Cited by 141 · see citing works
Gutzeit, C., Nagy, N., Gentile, M., Lyberg, K., Gumz, J., Vallhov, H., Puga, I., Klein, E., Gabrielsson, S., Cerutti, A., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302068 · Cited by 129 · see citing works
Shannon-Lowe, C. D., Adland, E., Bell, A. I., Delecluse, H., Rickinson, A. B., & Rowe, M. (2009) · Journal of Virology · doi:10.1128/jvi.00108-09 · Cited by 129 · see citing works
TRAF6 is a critical mediator of signal transduction by the viral oncogene latent membrane protein 1
Schultheiß, U., Püschner, S., Kremmer, E., Mak, T. W., Engelmann, H., Hammerschmidt, W., & Kieser, A. (2001) · The EMBO Journal · doi:10.1093/emboj/20.20.5678 · Cited by 121 · see citing works
Allday, M. J. (2009) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2009.07.007 · Cited by 109 · see citing works
What’s the Damage? The Impact of Pathogens on Pathways that Maintain Host Genome Integrity
Weitzman, M. D., & Weitzman, J. B. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.02.010 · Cited by 110 · see citing works
Brinkmann, M. M., & Schulz, T. F. (2006) · Journal of General Virology · doi:10.1099/vir.0.81598-0 · Cited by 107 · see citing works
Epstein-Barr virus LMP1 blocks p16INK4a–RB pathway by promoting nuclear export of E2F4/5
Ohtani, N., Brennan, P., Gaubatz, S., Sanij, E., Hertzog, P. J., Wolvetang, E. J., Ghysdael, J., Rowe, M., & Hara, E. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200302085 · Cited by 103 · see citing works
Vo, Q. N., Geradts, J., Gulley, M. L., Boudreau, D. A., Bravo, J. C., & Schneider, B. (2002) · Journal of Clinical Pathology · doi:10.1136/jcp.55.9.669 · Cited by 84 · see citing works
Regulation of the retinoblastoma proteins by the human herpesviruses
Hume, A. J., & Kalejta, R. F. (2009) · Cell Division · doi:10.1186/1747-1028-4-1 · Cited by 84 · see citing works
New Look of EBV LMP1 Signaling Landscape
Wang, L., & Ning, S. (2021) · Cancers · doi:10.3390/cancers13215451 · Cited by 84 · see citing works
Liu, M., Chang, Y., Chen, S., Chuang, Y.-C., Chen, Y., Lin, C., & Chen, J. (2004) · Oncogene · doi:10.1038/sj.onc.1208319 · Cited by 77 · see citing works
Collagenase‐resistant collagen promotes mouse aging and vascular cell senescence
Vafaie, F., Yin, H. R., O’Neil, C. H., Nong, Z., Watson, A., Arpino, J., Chu, M. W. A., Holdsworth, D. W., Gros, R., & Pickering, J. G. (2013) · Aging Cell · doi:10.1111/acel.12155 · Cited by 73 · see citing works
Eliopoulos, A. G., Waites, E. R., Blake, S. M. S., Davies, C. C., Murray, P. G., & Young, L. S. (2002) · Journal of Virology · doi:10.1128/jvi.77.2.1316-1328.2003 · Cited by 69 · see citing works
Loss of p16 expression has prognostic significance in human nasopharyngeal carcinoma.
Mäkitie, A. A., MacMillan, C., Ho, J., Shi, W., Lee, A. H., O’Sullivan, B., Payne, D. G., Pintilie, M., Cummings, B., Waldron, J. N., et al. (2003) · PubMed · Cited by 63 · see citing works
Eliopoulos, A. G., Davies, C. C., Blake, S. M. S., Murray, P. G., Najafipour, S., Tsichlis, P. N., & Young, L. S. (2002) · Journal of Virology · doi:10.1128/jvi.76.9.4567-4579.2002 · Cited by 61 · see citing works
Stevenson, D., Charalambous, C., & Wilson, J. B. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0591 · Cited by 61 · see citing works
RECK is a target of Epstein–Barr virus latent membrane protein 1
Liu, L., Peng, J., Chang, H., & Hung, W. (2003) · Oncogene · doi:10.1038/sj.onc.1207157 · Cited by 59 · see citing works
Najjar, I., Baran‐Marszak, F., Clorennec, C. L., Laguillier, C., Schischmanoff, P. O., Youlyouz‐Marfak, I., Schlee, M., Bornkamm, G. W., Raphaël, M., Feuillard, J., et al. (2005) · Journal of Virology · doi:10.1128/jvi.79.8.4936-4943.2005 · Cited by 57 · see citing works
Wang, J., Zheng, X., Qin, Z., Wei, L., Lu, Y., Qiu, P., Gao, Y., Zhang, X., Zhang, X., Li, Z., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.006853 · Cited by 57 · see citing works
The struggle of a good friend getting old: cellular senescence in viral responses and therapy
Kohli, J., Veenstra, I., & Demaria, M. (2021) · The EMBO Reports · doi:10.15252/embr.202052243 · Cited by 52 · see citing works
The Interaction of Viruses with the Cellular Senescence Response
Seoane, R., Vidal, S., Bouzaher, Y. H., El Motiam, A., & Rivas, C. (2020) · Biology · doi:10.3390/biology9120455 · Cited by 49 · see citing works
Cellular Senescence Markers p16INK4a and p21CIP1/WAF Are Predictors of Hodgkin Lymphoma Outcome
Caliò, A., Zamò, A., Ponzoni, M., Zanolin, M. E., Ferreri, A. J. M., Pedron, S., Montagna, L., Parolini, C., Fraifeld, V. E., Wolfson, M., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0508 · Cited by 47 · see citing works
EBV Infection and Its Regulated Metabolic Reprogramming in Nasopharyngeal Tumorigenesis
Yang, T., You, C., Meng, S., Lai, Z., Ai, W., & Zhang, J. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.935205 · Cited by 45 · see citing works
Senescence and Host–Pathogen Interactions
Humphreys, D., ElGhazaly, M., & Frisan, T. (2020) · Cells · doi:10.3390/cells9071747 · Cited by 40 · see citing works
Prognostic value of p16 expression in Epstein‐Barr virus–positive nasopharyngeal carcinomas
Jiang, W., Chamberlain, P. D., Garden, A. S., Kim, B. Y. S., Ma, D., Lo, E. J., Bell, D., Gunn, G. B., Fuller, C. D., Rosenthal, D. I., et al. (2015) · Head & Neck · doi:10.1002/hed.24258 · Cited by 37 · see citing works
Lee, S. W., Sakakibara, S., Maruo, S., Zhao, B., Calderwood, M. A., Holthaus, A. M., Lai, C.-Y., Takada, K., Kieff, E. D., & Johannsen, E. (2009) · Journal of Virology · doi:10.1128/jvi.01403-09 · Cited by 36 · see citing works
Liu, Y., Wang, X., Lo, A. K. F., Wong, Y. C., Cheung, A. L. M., & Tsao, S. W. (2001) · Journal of Medical Virology · doi:10.1002/jmv.2112 · Cited by 29 · see citing works
Tiwari, D., Mittal, N., & Jha, H. C. (2022) · Current Research in Neurobiology · doi:10.1016/j.crneur.2022.100046 · Cited by 27 · see citing works
Deregulation of the Cell Cycle by the Epstein–Barr Virus
O’Nions, J., & Allday, M. J. (2004) · Advances in cancer research · doi:10.1016/s0065-230x(04)92006-4 · Cited by 27 · see citing works
Pathogenesis and therapeutic implications of EBV-associated epithelial cancers
Low, Y. H., Loh, C. J. L., Peh, D. Y. Y., Chu, A. J. M., Han, S., & Toh, H. C. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1202117 · Cited by 26 · see citing works
Yip, Y., Tsang, C., Deng, W., Cheung, P.-Y. P., Jin, Y., Cheung, A. L. M., Lung, M. L., & Tsao, S. (2010) · Journal of Medical Virology · doi:10.1002/jmv.21875 · Cited by 25 · see citing works
Kim, L., Peh, S., & Poppema, S. (2005) · Human Pathology · doi:10.1016/j.humpath.2005.09.028 · Cited by 24 · see citing works
Egr‐1, a new downstream molecule of Epstein‐Barr virus latent membrane protein 1
Kim, J. H., Kim, W. S., Kang, J. H., Lim, H.-Y., Ko, Y. H., & Park, C. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.01.020 · Cited by 24 · see citing works
Liu, X., Deng, Y., Huang, Y., Ye, J., Xie, S., He, Q., Chen, Y., Lin, Y., Liang, R., Wei, J., et al. (2022) · Current Oncology · doi:10.3390/curroncol29090475 · Cited by 22 · see citing works
Signal transduction by the Epstein‐Barr virus oncogene latent membrane protein 1 (LMP1)
Kieser, A. (2007) · Signal Transduction · doi:10.1002/sita.200600116 · Cited by 21 · see citing works
The Molecular Basis for the Generation of Hodgkin and Reed-Sternberg Cells in Hodgkin’s Lymphoma
Lee, I., Kim, S. H., Song, H. G., & Park, S. H. (2003) · International Journal of Hematology · doi:10.1007/bf02982639 · Cited by 21 · see citing works
Kim, J. H., Kim, W. S., & Park, C. (2008) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428190802087454 · Cited by 19 · see citing works
Kim, J. H., Kim, W. S., Yun, Y., & Park, C. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2010.07.013 · Cited by 18 · see citing works
Xin, B., He, Z., Yang, X., Chan, C.-P., Ng, M., & Cao, L. (2001) · Journal of Virology · doi:10.1128/jvi.75.6.3010-3015.2001 · Cited by 18 · see citing works
Self-citationMacDiarmid, J. A., Stevenson, D., Campbell, D. H., & Wilson, J. B. (2003) · Carcinogenesis · doi:10.1093/carcin/bgg070 · Cited by 17 · see citing works
Shafqat, A., Masters, M. C., Tripathi, U., Tchkonia, T., Kirkland, J. L., & Hashmi, S. K. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102400 · Cited by 15 · see citing works
DNA damage checkpoints in nasopharyngeal carcinoma
Poon, R. Y. C. (2014) · Oral Oncology · doi:10.1016/j.oraloncology.2014.01.009 · Cited by 15 · see citing works
Long, X., Li, Y., Yang, M., Huang, L., Gong, W., & Kuang, E. (2016) · Journal of Virology · doi:10.1128/jvi.00999-16 · Cited by 14 · see citing works
Evasion of oncogene-induced senescence by gammaherpesviruses
Leidal, A. M., Pringle, E. S., & McCormick, C. (2012) · Current Opinion in Virology · doi:10.1016/j.coviro.2012.09.009 · Cited by 13 · see citing works
Senotherapeutics: An emerging approach to the treatment of viral infectious diseases in the elderly
Li, Z., Tian, M., Wang, G., Cui, X., Ma, J., Liu, S., Shen, B., Liu, F., Wu, K., Xiao, X., et al. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1098712 · Cited by 13 · see citing works
Trapp-Fragnet, L., Schermuly, J., Kohn, M., Bertzbach, L. D., Pfaff, F., Denesvre, C., Kaufer, B. B., & Härtle, S. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1010006 · Cited by 11 · see citing works
Loss of p16/CDKN2A Protein in Epstein-Barr Virus-Associated Gastric Carcinoma
Koriyama, C., Kitajima, S., Nomoto, M., Sueyoshi, K., Itoh, T., Eizuru, Y., Yonezawa, S., & Akiba, S. (2004) · Oncology · doi:10.1159/000080290 · Cited by 11 · see citing works
Bob-1 is expressed in classic Hodgkin lymphoma
All, H. S. A. E. (2007) · Diagnostic Pathology · doi:10.1186/1746-1596-2-10 · Cited by 8 · see citing works
p16INK4A-independence of Epstein–Barr virus-induced cell proliferation and virus latency
Hayes, M. J., Koundouris, A., Gruis, N. A., Bergman, W., Peters, G. G., & Sinclair, A. J. (2004) · Journal of General Virology · doi:10.1099/vir.0.79831-0 · Cited by 7 · see citing works
Adili, A., O’Connor, T., Wales, P., Seemann, M. D., Höller, S., Hummer, B., Freiberger, S. N., Rauthe, S., & Rupp, N. J. (2023) · Head and Neck Pathology · doi:10.1007/s12105-023-01592-4 · Cited by 3 · see citing works
Irshaid, F. I., Tarawneh, K. A., Alshdefat, A., Dilmi, F., Jaran, A., Al-Hadithi, R. H., & Al-Khatib, A. (2013) · Europe PMC (PubMed Central) · Cited by 2 · see citing works
KSHV Latency in Transformed B-cells: The Role of LANA1 as a Therapeutic Target
Côrte‐Real, S., Fonseca, L., & Gonçalves, J. (2008) · Virology Research and Treatment · doi:10.4137/vrt.s631 · Cited by 1 · see citing works
The Biology and Molecular Biology Underlying Epstein-Barr Virus Oncogenesis
Martin, H. J., & Hayward, S. D. (2008) · Translational research in biomedicine · doi:10.1159/000141037
EBV membrane protein LMP2A interactions with ubiquitin ligases and a signaling scaffold
Matskova, L. (2004) · Figshare
Mechanism and significance of cell senescence induced by viral infection
Chang, Y., Wu, X., Deng, L., Wang, S., & Mao, G. (2025) · Journal of Zhejiang University (Medical Sciences) · doi:10.3724/zdxbyxb-2024-0213
Regulation von Apoptose und Überleben durch Signalwege von LMP1 und TNF-Rezeptor 1
Neugebauer, J. K. (2007) · Elektronische Hochschulschriften der LMU München (Ludwig-Maximilians-Universität München) · doi:10.5282/edoc.7974
Cudejko, C. (2010) · doi:10.70675/3be56540zf3b1z4ee1z99ffz2dbbe7a0dc17
Modulation of DNA Damage by Epstein–Barr Virus (EBV)
DiMaulo-Milk, E., & Damania, B. (2026) · Viruses · doi:10.3390/v18091035
- Authors
- Yang, X., He, Z., Xin, B., & Cao, L.
- Affiliations
- University of Hong Kong (HK)
- ORCID
- Cao, Liang
- Venue
- Oncogene
- Published
- 2000-04-13
- Volume
- 19
- Issue
- 16
- Pages
- 2002-2013
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2314609747
- Cited by
- 71
- References
- 62
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 1 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Croucher Foundation
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- Epstein-Barr virus, replicative senescence, premature senescence, p16INK4a, p21, oncogenic Ras, cell immortalization, mouse embryonic fibroblasts, Saos-2 cells, carcinogenesis
- MeSH terms
- Animals, Cell Division, Cell Line, Cell Line, Transformed, Diploidy, Embryo, Mammalian, Female, Fibroblasts, Gene Expression Regulation, Humans, Mice, Inbred BALB C, Promoter Regions, Genetic, Genes, ras, Transfection, Viral Matrix Proteins, Cyclins, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p21, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
