Retinoic acid induces persistent, RAR?-mediated anti-proliferative responses in Epstein-Barr virus-immortalized b lymphoblasts carrying an activated c-myc oncogene but not in Burkitt's lymphoma cell lines

2000 ◽  
Vol 86 (3) ◽  
pp. 375-384 ◽  
Author(s):  
Roberta Cariati ◽  
Paola Zancai ◽  
Michele Quaia ◽  
Giovanna Cutrona ◽  
Franca Giannini ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Burkitt’S Lymphoma ◽  
Lymphoma Cell ◽  
Burkitt's Lymphoma ◽  
Myc Oncogene ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals The bfl-1 Gene Is Transcriptionally Upregulated by the Epstein-Barr Virus LMP1, and Its Expression Promotes the Survival of a Burkitt's Lymphoma Cell Line

2000 ◽  
Vol 74 (14) ◽  
pp. 6652-6658 ◽  
Author(s):  
Brendan D'Souza ◽  
Martin Rowe ◽  
Dermot Walls
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Burkitt’S Lymphoma ◽  
Lymphoma Cell ◽  
Burkitt's Lymphoma ◽  
Type I ◽  
Lymphoma Cell Line ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACT The recently identified bfl-1 gene (also known asA1 or GRS), a homologue of bcl-2, encodes an antiapoptotic protein that suppresses apoptosis induced by the p53 tumor suppressor protein and exhibits proliferative and potent cooperative transforming activities. We show that elevated levels of bfl-1 mRNA are a feature of Epstein-Barr virus (EBV)-immortalized B-cell lines and Burkitt's lymphoma cell lines expressing the full spectrum of EBV latent proteins. Using an EBV-negative Burkitt's lymphoma cell line in which the expression of EBV latent membrane protein 1 (LMP1) is inducibly regulated by tetracycline, we demonstrate that LMP1 expression coincides with a dramatic increase in the level ofbfl-1 mRNA. Also in this system, an increase in the level of Bcl-2 protein was seen to occur earlier than that ofbcl-2 mRNA, suggesting that both transcriptional and translational mechanisms are involved in the control of Bcl-2 expression by LMP-1. We show that elevated bfl-1mRNA stability can contribute to this effect of LMP-1, thus providing evidence of a novel mechanism of gene regulation by this EBV protein. Upregulation ofbfl-1 by LMP1 was not observed in the T-cell line Jurkat or the epithelial cell line C33A. Ectopic expression of Bfl-1 in an EBV-positive cell line exhibiting a latency type I infection protects against apoptosis induced by growth factor deprivation, thereby providing a functional role for Bfl-1 in this cellular context and adding Bfl-1 to the list of antiapoptotic proteins whose expression is modulated by EBV. This is the first report of the regulation of bfl-1expression by a viral protein, and this novel finding may thus represent an important link between the EBV oncoprotein LMP1 and its cellular growth-transforming properties.

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