The c-Cbl proto-oncoprotein downregulates EBV LMP2A signaling

Masato Ikeda, Richard Longnecker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV) plays a key role in regulating viral latency and EBV pathogenesis by functionally mimicking signals induced by the B-cell receptor (BCR) altering normal B cell development. As c-Cbl ubiquitin ligase (E3) is a critical negative regulator in the BCR signal pathway, the role of c-Cbl in the function and formation of the LMP2A signalosome was examined. c-Cbl promoted LMP2A degradation through ubiquitination, specifically degraded the Syk protein tyrosine kinase in the presence of LMP2A, and inhibited LMP2A induction of the EBV lytic cycle. Our earlier studies indicated that LMP2A-dependent Lyn degradation was mediated by Nedd4-family E3s in LMP2A expressing cells. Combine with these new findings, we propose a model in which c-Cbl and Nedd4-family E3s cooperate to degrade target proteins at discrete steps in the function of the LMP2A signalosome.

Original languageEnglish (US)
Pages (from-to)183-191
Number of pages9
JournalVirology
Volume385
Issue number1
DOIs
StatePublished - Mar 1 2009

Keywords

  • Epstein-Barr virus (EBV)
  • Latent membrane protein 2A (LMP2A)
  • Lyn
  • Lytic replication
  • Syk
  • Ubiquitin
  • c-Cbl

ASJC Scopus subject areas

  • Virology

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