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  • Original Paper
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The amino-terminus and membrane-spanning domains of LMP-1 inhibit cell proliferation

Abstract

The LMP-1 oncoprotein of EBV is required to maintain proliferation of infected B-cells and shares several features with CD40, TNF-R1, and related receptors. Members of this family can bind TRAF and TRADD molecules and activate NF-κB and AP-1, as can LMP-1. While CD40 and TNF-R1 are dependent on binding their ligands for their signaling, LMP-1 apparently is not. We have found that LMP-1 can act as a governor of cell proliferation and thereby limit its own activities. Its inhibition of proliferation is not mediated by apoptosis but results in cytostasis in four cell lines tested. The structural moiety of LMP-1 that distinguishes it from CD40 and TNF-R1, its amino-terminus and multiple membrane spanning segments, alone can mediate its cytostatic activity.

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Acknowledgements

We thank Ashok Aiyar, Paul Lambert, David Mackey and Mary Ellen Perry for their critical review of this manuscript. We also thank Elizabeth R Leight for performing some of the long-term assays for inhibition of cell proliferation and Tim Bloss and Wolfgang Hammerschmidt for constructing some of the vectors we studied. This work was supported by Public Health Service grants CA-22443, CA-07175, T32-CA-09135, and CA-70723.

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Kaykas, A., Sugden, B. The amino-terminus and membrane-spanning domains of LMP-1 inhibit cell proliferation. Oncogene 19, 1400–1410 (2000). https://doi.org/10.1038/sj.onc.1203365

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