Epstein-Barr Virus latent membrane protein 1 overcomes all-trans retinoic acid-induced apoptosis by inhibiting retinoic acid receptor- beta 2 expression

Nasopharyngeal carcinoma is closely associated with infection with Epstein-Barr Virus (EBV); however, the mechanism is still unclear. Here, we report that the EBV oncoprotein, latent membrane protein 1 (LMP1), suppresses apoptotic cell death provoked by all-trans retinoic acid (ATRA) in NPC cells. F...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2012-06, Vol.423 (2), p.313-318
Main Authors: Lee, Hyehyeon, Seo, So Young, Tiwari, Indira, Jang, Kyung Lib
Format: Article
Language:English
Subjects:
Apoptosis
BAK protein
Caspase-3
Caspase-8
Caspase-9
DNA methylation
Epstein-Barr virus
Gene expression
Infection
Latent membrane protein 1
Nasopharyngeal carcinoma
Poly(ADP-ribose) polymerase
Retinoic acid receptors
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Summary:Nasopharyngeal carcinoma is closely associated with infection with Epstein-Barr Virus (EBV); however, the mechanism is still unclear. Here, we report that the EBV oncoprotein, latent membrane protein 1 (LMP1), suppresses apoptotic cell death provoked by all-trans retinoic acid (ATRA) in NPC cells. For this purpose, LMP1 downregulated levels of Bak whilst it upregulated levels of Bcl2, lowering the ratio of Bak to Bcl2. In addition, LMP1 suppressed ATRA-mediated activation of Caspase 9, Caspase 3, and PARP but not Caspase 8 in Ad-AH cells, suggesting that LMP1 acts by blocking the activation of intrinsic apoptosis pathway by ATRA. These effects were almost completely abolished when levels of retinoic acid receptor- beta 2 (RAR- beta 2) in the LMP1-expressing cells were recovered by either exogenous gene expression or treatment with a universal DNMT inhibitor, 5-Aza-2'dC, indicating that LMP1 executes its antiapoptotic effects by downregulating levels of RAR- beta 2 via DNA methylation.
ISSN:0006-291X
DOI:10.1016/j.bbrc.2012.05.118