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 language | English (US) |
|---|---|
| Pages (from-to) | 183-191 |
| Number of pages | 9 |
| Journal | Virology |
| Volume | 385 |
| Issue number | 1 |
| DOIs | |
| State | Published - Mar 1 2009 |
Funding
R.L. is John Edward Porter Professor in Biomedical Research and supported by the Public Health Service grants CA62234 and CA73507 from the National Cancer Institute.
Keywords
- Epstein-Barr virus (EBV)
- Latent membrane protein 2A (LMP2A)
- Lyn
- Lytic replication
- Syk
- Ubiquitin
- c-Cbl
ASJC Scopus subject areas
- Virology
