Antiproliferative function of glia maturation factor beta.

Lim, Ramón; Zhong, Weixiong; Zaheer, Asgar

doi:10.1091/mbc.1.10.741

Cited by 16 publications

(8 citation statements)

References 24 publications

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“…This difference in the tightness of regulation is also evident from the thymidine incorporation assays, in which the difference between the uninduced and the induced states is consistently larger for EREB2-5 than for P493-6 cells (data not shown). All proteins identified are newly synthesized upon EBNA2 activation or c-Myc induction, as they were detected following 35 S labeling. Identification of EBNA2 target proteins that are not regulated by c-Myc in P493-6 cells.…”

Section: Resultsmentioning

confidence: 95%

“…Gel spots from 35 S autoradiographs or silver-stained gels were quantified by using PDQuest software and differentially regulated target proteins identified by MALDI-TOF mass spectrometry from tryptic digests in combination with peptide mass fingerprinting. Target proteins reproducibly regulated upon activation of EBNA2 are shown in autoradiographs of selected sections (pI 4 to 7.5) of 2D gels from 35 Slabeled total cell lysates of EREB2-5 and P493-6 cells without or with estrogen (8 h) and with or without tetracycline (8 h), respectively ( Fig. 1), and are described in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…Infection with EBV resulted in a continuous increase of thymidine incorporation (six-to eightfold at day 5 after infection) in comparison to noninfected primary B cells (data not shown). A substantial increase in thymidine incorporation was observed 35 S-labeled whole-cell lysates (35S) or from silver-stained gels (silverstain). The induction level equals the value for the induced situation divided by that for the noninduced situation.…”

Section: Resultsmentioning

confidence: 99%

“…Two-dimensional gels with 35 S-labeled proteins were exposed to X-ray films (Kodak X-OMAT AR). The films or silver-stained gels were scanned, and digital images were analyzed for changes in protein patterns with the image analysis software PDQuest (BioRad).…”

Section: Methodsmentioning

confidence: 99%

“…Soluble recombinant GMF␤ inhibits the proliferation of neoplastic cells in culture by arresting them in the G 0 /G 1 phase (35). It may be speculated that hGMF␥ might fulfill similar functions during B-cell immortalization by EBV.…”

Section: Vol 78 2004mentioning

confidence: 99%

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Identification of Epstein-Barr Virus (EBV) Nuclear Antigen 2 (EBNA2) Target Proteins by Proteome Analysis: Activation of EBNA2 in Conditionally Immortalized B Cells Reflects Early Events after Infection of Primary B Cells by EBV

Schlee

Krug

Gires

et al. 2004

J Virol

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The Epstein-Barr virus (EBV) is a ubiquitous B-lymphotropic herpesvirus associated with several malignant tumors, e.g., Burkitt's lymphoma and Hodgkin's disease, and is able to efficiently immortalize primary B lymphocytes in vitro. The growth program of infected B cells is initiated and maintained by the viral transcription factor EBV nuclear antigen 2 (EBNA2), which regulates viral and cellular genes, including the proto-oncogene c-myc. In our study, patterns of protein expression in B cells with and without EBNA2 were analyzed by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. For this purpose, we used a conditional immortalization system for EBV, a B cell line (EREB2-5) that expresses an estrogen receptor-EBNA2 fusion protein. In order to discriminate downstream targets of c-Myc from c-Myc-independent EBNA2 targets, we used an EREB2-5-derived cell line, P493-6, in which c-Myc is expressed under the control of a tetracycline-regulated promoter. Of 20 identified EBNA2 target proteins, 11 were c-Myc dependent and therefore most probably associated with proliferation, and one of these proteins was a posttranslationally modified protein, i.e., hypusinylated eIF5a. Finally, to estimate the relevance of EBNA2 targets during early EBV infection, we analyzed the proteomes of primary B cells before and after infection with EBV. The protein expression pattern induced upon EBV infection was similar to that following EBNA2 activation. These findings underscore the value of EREB2-5 cells as an appropriate model system for the analysis of early events in the process of EBV-mediated B-cell immortalization.Epstein-Barr virus (EBV) is a ubiquitous B-lymphotropic herpesvirus that after a usually asymptomatic infection is carried by more than 90% of adults for the rest of their lives. When the primary infection is postponed to late childhood or adolescence, EBV can cause infectious mononucleosis. The virus has been linked to the development of several malignant tumors, including Burkitt's lymphoma, Hodgkin's disease, lymphoproliferative disease in immunosuppressed individuals, certain forms of T-cell lymphoma, and some lymphoepithelial tumors, such as nasopharyngeal carcinoma and a proportion of gastric cancers (reviewed in reference 4). Infection of primary B cells with EBV in vitro causes the activation of the cells and drives them into continuous proliferation, a process termed immortalization. Cell lines established by infection of primary human B cells with EBV are called lymphoblastoid cell lines (LCLs).The first viral genes expressed in EBV-infected B cells are EBNA2 and EBNA-LP, two nuclear antigens that act as transcription activators in concert with each other and regulate the expression of viral as well as cellular genes involved in the initiation and maintenance of cell proliferation. EBNA2 in conjunction with EBNA-LP upregulates the expression of the viral membrane latent genes LMP1 and LMP2 and regulates the BamHI-C promoter driving the expression of all nuclear antigens (reviewed in refe...

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Vol 78 2004mentioning

confidence: 99%

See 3 more Smart Citations