| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 155, Issue 3 1047-1056, Copyright © 1995 by American Association of Immunologists
ARTICLES |
L Arvanitakis, N Yaseen and S Sharma
Department of Pathology, Roger Williams Medical Center-Brown University, Providence, RI 02908, USA.
The normal cell cycle is regulated by several molecules, such as the tumor-suppressor protein pRb, the G1 cyclins, the cyclin-dependent kinases, and their inhibitors. These regulators are targeted by negative growth regulatory signals, such as that provided by TGF-beta. Here, we show that the presence of either wild-type EBV or its transforming latent membrane protein-1 (LMP-1) results in the loss of TGF-beta 1-mediated growth inhibition in human B cells. Chemical cross- linking with 125I-labeled TGF-beta 1 showed an essentially normal TGF- beta receptor profile in EBV-positive and EBV-negative Burkitt's lymphoma cell lines, and these receptors were shown to be functional in transducing signals, as evidenced by the TGF-beta 1-mediated modulation of junB gene expression. However, TGF-beta 1 did not induce dephosphorylation of pRb in EBV (or LMP-1)-positive cells as opposed to EBV-negative cells, suggesting a dichotomy in the TGF-beta 1 signaling pathway leading to separable gene regulatory and growth inhibitory responses. Furthermore, LMP-1 was found to induce the expression of cyclin D2; normal B cells or EBV-negative Burkitt's lymphoma cells do not express D-type cyclins. Taken together, these data point to a potential mechanism underlying EBV-mediated B cell transformation whereby constitutive induction of key cell cycle regulators by LMP-1 can lead to pRb hyperphosphorylation and uncontrolled cell proliferation.
This article has been cited by other articles:
|
|
 |
|
  B. G. Bajaj, M. Murakami, Q. Cai, S. C. Verma, K. Lan, and E. S. Robertson Epstein-Barr Virus Nuclear Antigen 3C Interacts with and Enhances the Stability of the c-Myc Oncoprotein J. Virol., April 15, 2008; 82(8): 4082 - 4090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Mainou and N. Raab-Traub LMP1 Strain Variants: Biological and Molecular Properties. J. Virol., July 1, 2006; 80(13): 6458 - 6468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Clybouw, B. Mchichi, S. Mouhamad, M. T. Auffredou, M. F. Bourgeade, S. Sharma, G. Leca, and A. Vazquez EBV Infection of Human B Lymphocytes Leads to Down-Regulation of Bim Expression: Relationship to Resistance to Apoptosis J. Immunol., September 1, 2005; 175(5): 2968 - 2973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Seo, J. Park, and J. Choe Kaposi's Sarcoma-Associated Herpesvirus Viral IFN Regulatory Factor 1 Inhibits Transforming Growth Factor-{beta} Signaling Cancer Res., March 1, 2005; 65(5): 1738 - 1747. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hleb, S. Murphy, E. F. Wagner, N. N. Hanna, N. Sharma, J. Park, X. C. Li, T. B. Strom, J. F. Padbury, Y.-T. Tseng, et al. Evidence for Cyclin D3 as a Novel Target of Rapamycin in Human T Lymphocytes J. Biol. Chem., July 23, 2004; 279(30): 31948 - 31955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Eliopoulos, E. R. Waites, S. M. S. Blake, C. Davies, P. Murray, and L. S. Young TRAF1 Is a Critical Regulator of JNK Signaling by the TRAF-Binding Domain of the Epstein-Barr Virus-Encoded Latent Infection Membrane Protein 1 but Not CD40 J. Virol., December 20, 2002; 77(2): 1316 - 1328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu, A. Ahmad, and J. Menezes Preferential Localization of the Epstein-Barr Virus (EBV) Oncoprotein LMP-1 to Nuclei in Human T Cells: Implications for Its Role in the Development of EBV Genome-Positive T-Cell Lymphomas J. Virol., March 19, 2002; 76(8): 4080 - 4086. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. B. Keerthisingam, R. G. Jenkins, N. K. Harrison, N. A. Hernandez-Rodriguez, H. Booth, G. J. Laurent, S. L. Hart, M. L. Foster, and R. J. McAnulty Cyclooxygenase-2 Deficiency Results in a Loss of the Anti-Proliferative Response to Transforming Growth Factor-{beta} in Human Fibrotic Lung Fibroblasts and Promotes Bleomycin-Induced Pulmonary Fibrosis in Mice Am. J. Pathol., April 1, 2001; 158(4): 1411 - 1422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Höfelmayr, L. J. Strobl, G. Marschall, G. W. Bornkamm, and U. Zimber-Strobl Activated Notch1 Can Transiently Substitute for EBNA2 in the Maintenance of Proliferation of LMP1-Expressing Immortalized B Cells J. Virol., March 1, 2001; 75(5): 2033 - 2040. [Abstract] [Full Text]
|
|
|
|
 |
|
 P G Murray and L S Young Themed issue: the biology and pathology of the Epstein-Barr virus Mol. Pathol., October 1, 2000; 53(5): 219 - 221. [Full Text]
|
|
|
|
|
|
J Nicholas Evolutionary aspects of oncogenic herpesviruses Mol. Pathol., October 1, 2000; 53(5): 222 - 237. [Abstract] [Full Text]
|
|
|
|
|
|
L. F. van Dyk, H. W. Virgin IV, and S. H. Speck The Murine Gammaherpesvirus 68 v-Cyclin Is a Critical Regulator of Reactivation from Latency J. Virol., August 15, 2000; 74(16): 7451 - 7461. [Abstract] [Full Text]
|
|
|
|
|
|
A. T. Hoge, S. B. Hendrickson, and W. H. Burns Murine Gammaherpesvirus 68 Cyclin D Homologue Is Required for Efficient Reactivation from Latency J. Virol., August 1, 2000; 74(15): 7016 - 7023. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. J. Inman and M. J. Allday Resistance to TGF-{beta}1 correlates with a reduction of TGF-{beta} type II receptor expression in Burkitt's lymphoma and Epstein-Barr virus-transformed B lymphoblastoid cell lines J. Gen. Virol., June 1, 2000; 81(6): 1567 - 1578. [Abstract] [Full Text]
|
|
|
|
|
|
A. Martin, F. Baran-Marzak, S. El Mansouri, C. Legendre, V. Leblond, F. Charlotte, F. Davi, D. Canioni, and M. Raphael Expression of p16/INK4a in Posttransplantation Lymphoproliferative Disorders Am. J. Pathol., May 1, 2000; 156(5): 1573 - 1579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu, A. Ahmad, M. D'Addario, L. Knafo, J. F. Jones, U. Prasad, R. Dolcetti, E. Vaccher, and J. Menezes Analysis and Significance of Anti-Latent Membrane Protein-1 Antibodies in the Sera of Patients with EBV-Associated Diseases J. Immunol., March 1, 2000; 164(5): 2815 - 2822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Santiago, E. Clark, S. Chong, C. Molina, F. Mozafari, R. Mahieux, M. Fujii, N. Azimi, and F. Kashanchi Transcriptional Up-Regulation of the Cyclin D2 Gene and Acquisition of New Cyclin-Dependent Kinase Partners in Human T-Cell Leukemia Virus Type 1-Infected Cells J. Virol., December 1, 1999; 73(12): 9917 - 9927. [Abstract] [Full Text]
|
|
|
|
|
|
L. F. van Dyk, J. L. Hess, J. D. Katz, M. Jacoby, S. H. Speck, and H. W. Virgin IV The Murine Gammaherpesvirus 68 v-Cyclin Gene Is an Oncogene That Promotes Cell Cycle Progression in Primary Lymphocytes J. Virol., June 1, 1999; 73(6): 5110 - 5122. [Abstract] [Full Text]
|
|
|
|
|
|
V. L. Zacny, J. Wilson, and J. S. Pagano The Epstein-Barr Virus Immediate-Early Gene Product, BRLF1, Interacts with the Retinoblastoma Protein during the Viral Lytic Cycle J. Virol., October 1, 1998; 72(10): 8043 - 8051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. F. Wagner, M. Hleb, N. Hanna, and S. Sharma A Pivotal Role of Cyclin D3 and Cyclin-Dependent Kinase Inhibitor p27 in the Regulation of IL-2-, IL-4-, or IL-10-Mediated Human B Cell Proliferation J. Immunol., August 1, 1998; 161(3): 1123 - 1131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gangappa, L. F. van Dyk, T. J. Jewett, S. H. Speck, and H. W. Virgin IV Identification of the In Vivo Role of a Viral bcl-2 J. Exp. Med., April 1, 2002; 195(7): 931 - 940. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
