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Ubiquitination of the Epstein–Barr virus-encoded latent membrane protein 1 depends on the integrity of the TRAF binding site

Oncogene volume 22, pages 5614–5618 (2003)Cite this article

Abstract

The latent membrane protein 1 (LMP1) encoded by the Epstein–Barr virus functions as a constitutively activated receptor of the tumor necrosis factor receptor family. LMP1 is a short-lived protein that is ubiquitinated and degraded by the proteasome. We have previously shown that LMP1 recruits the adapter protein tumor necrosis factor receptor-associated factor 3 (TRAF3) to lipid rafts. To test if TRAFs are involved in LMP1's ubiquitination, we have mutated the LMP1 CTAR1 site that has been identified as a TRAF binding site. We show that the CTAR1 mutant (CTAR1−) is expressed after transfection at a similar level to wild-type LMP1, and behaves as wild-type LMP1 with respect to membrane localization. However, CTAR1− does not bind TRAF3. We demonstrate that ubiquitination of CTAR1− is significantly reduced when compared to wild-type LMP1. In addition, the expression of wild-type LMP1 induces the ubiquitination, an effect that is significantly reduced when the CTAR1− is expressed. Taken together, our results suggest that TRAF proteins are involved in the ubiquitination of LMP1, and that their binding to LMP1 may facilitate their own ubiquitination.

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Acknowledgements

The Swiss National Science Foundation (SNSF 31-61960.00) has supported this work. We thank Dr P Shaw and Dr M Thome for a critical reading of the manuscript.

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  1. Institute of Biochemistry, University of Lausanne, ch. des Boveresses 155, Epalinges, 1066, Switzerland

    Sylvia Rothenberger, Kimberly Burns, Marga Rousseaux, Jürg Tschopp & Claude Bron

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  1. Sylvia Rothenberger
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Correspondence to Sylvia Rothenberger.

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Rothenberger, S., Burns, K., Rousseaux, M. et al. Ubiquitination of the Epstein–Barr virus-encoded latent membrane protein 1 depends on the integrity of the TRAF binding site. Oncogene 22, 5614–5618 (2003). https://doi.org/10.1038/sj.onc.1206497

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