Structural Basis for Apoptosis Inhibition by Epstein-Barr Virus BHRF1
Details
Publication Year 2010-12, Volume 6, Issue #12, Page -
Journal Title
PLOS PATHOGENS
Publication Type
Journal Article
Abstract
Epstein-Barr virus (EBV) is associated with human malignancies, especially those affecting the B cell compartment such as Burkitt lymphoma. The virally encoded homolog of the mammalian pro-survival protein Bcl-2, BHRF1 contributes to viral infectivity and lymphomagenesis. In addition to the pro-apoptotic BH3-only protein Bim, its key target in lymphoid cells, BHRF1 also binds a selective sub-set of pro-apoptotic proteins (Bid, Puma, Bak) expressed by host cells. A consequence of BHRF1 expression is marked resistance to a range of cytotoxic agents and in particular, we show that its expression renders a mouse model of Burkitt lymphoma untreatable. As current small organic antagonists of Bcl-2 do not target BHRF1, the structures of it in complex with Bim or Bak shown here will be useful to guide efforts to target BHRF1 in EBV-associated malignancies, which are usually associated with poor clinical outcomes.
Publisher
PUBLIC LIBRARY SCIENCE
Keywords
PROGRAMMED CELL-DEATH; PROSURVIVAL BCL-2 PROTEINS; BH3 DOMAINS; TRANSGENIC MICE; BAX; HOMOLOG; FAMILY; MYC; BIM; LIGANDS
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2010-12-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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