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© The Rockefeller University Press, 0021-9525/2003/7/167-b $5.00
The Journal of Cell Biology, Volume 162, Number 2, 167-b-167

Kicking out antiviral proteins

LMP1 excludes E2F4 (red) from the nucleus (arrows).

Like a bouncer at a club, the Epstein Barr virus (EBV) LMP1 protein removes a threatening presence by ejecting cellular proteins from the nucleus, according to Ohtani et al. on page 173.

EBV infection leads to excessive cell proliferation that can cause disorders such as carcinoma and lymphoma. Cells normally prevent unusual proliferation by inducing the p16^INK4a/RB-dependent senescence pathway. But the authors show that EBV bypasses this failsafe by relocating transcription factors for this pathway to the cytoplasm.

Nuclear export was induced by the viral protein LMP1. EBV infection or LMP1 expression caused the export of Ets2, the inducer of p16^INK4a transcription. LMP1 also kicked out transcription factors E2F4 and E2F5, which normally act downstream of p16^INK4a to prevent cell cycle progression. LMP1 induces export of its targets by increasing their affinity for CRM1, which directs the major nuclear export pathway in mammalian cells. The molecular details are unclear as yet, but the authors find that the MEK pathway is required for E2F4 export. Perhaps phosphorylation of E2F4 makes it more attractive to CRM1.

Immortalization of human cells requires inactivation of both RB and p53 pathways, so LMP1 or another EBV protein may also cause the export of p53-related proteins. Ohtani et al. found that at least some other cell cycle proteins containing nuclear export signals are resistant to LMP1. If LMP1 targets only a few proteins for export, it might be possible to develop drugs to limit EBV infection with few side effects.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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Epstein-Barr virus LMP1 blocks p16^INK4a–RB pathway by promoting nuclear export of E2F4/5

Naoko Ohtani, Paul Brennan, Stefan Gaubatz, Elaine Sanij, Paul Hertzog, Ernst Wolvetang, Jacques Ghysdael, Martin Rowe, and Eiji Hara
J. Cell Biol. 2003 162: 173-183. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 793K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Article Social Bookmarking                            What's this?