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The latent membrane protein 1 oncogene modifies B-cell physiology by regulating autophagy

Oncogene volume 27, pages 2833–2842 (2008)Cite this article

Abstract

Epstein–Barr virus (EBV) is a herpes virus that is associated with several human cancers. Infection of B cells by EBV leads to their induction and maintenance of proliferation and requires the oncogene, latent membrane protein 1 (LMP1). LMP1 signals in a ligand-independent manner and is expressed at widely different levels in cells of a single clone. It is this unusual distribution that allows LMP1 to stimulate multiple, distinct pathways. Average levels of LMP1 induce proliferation while high levels induce cytostasis and inhibition of protein synthesis. These inhibitory pathways are induced by the six transmembrane domains of LMP1. We uncovered a novel function encoded by transmembrane domains 3–6 of LMP1; they induce autophagy in a dose-dependent manner and thus, modify the physiology of their host. Cells that express low levels of LMP1 display early stages of autophagy, autophagosomes; those that express high levels of this oncogene display late stages of autophagy, autolysosomes. Inhibition of autophagy in EBV-positive cells leads to an accumulation of LMP1 and a decreased ability to form colonies. These results indicate that LMP1's induction of autophagy contributes to its own regulation and that of its host cell.

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Acknowledgements

We thank Dr Takashi Ueno for kindly providing the antibody against LC3. We also thank Dr Marisa Otegui and Dr Tomomi Nakahara for valuable discussions. We are grateful to the Flow Cytometry Facility of the UW Paul P Carbone Comprehensive Cancer Center and the UW-Electron Microscope Facility. This work was supported by NIH grants CA070723 and P30 CA014520. Bill Sugden is an American Cancer Society Research Professor.

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  1. McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI, USA

    D Y Lee & B Sugden

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  1. D Y Lee
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  2. B Sugden
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Correspondence to B Sugden.

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Lee, D., Sugden, B. The latent membrane protein 1 oncogene modifies B-cell physiology by regulating autophagy. Oncogene 27, 2833–2842 (2008). https://doi.org/10.1038/sj.onc.1210946

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