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Structural basis for apoptosis inhibition by Epstein-Barr virus bhrf1
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نویسنده
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kvansakul m. ,wei a.h. ,fletcher j.i. ,willis s.n. ,chen l. ,roberts a.w. ,huang d.c.s. ,colman p.m.
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منبع
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plos pathogens - 2010 - دوره : 6 - شماره : 12
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چکیده
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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. & copy; 2010 kvansakul et al.
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آدرس
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the walter and eliza hall institute of medical research,parkville,victoria,australia,department of biochemistry,la trobe university,victoria, Australia, the walter and eliza hall institute of medical research,parkville,victoria,australia,department of clinical hematology,the alfred hospital and the australian centre for blood diseases,monash university,melbourne, Australia, the walter and eliza hall institute of medical research,parkville,victoria,australia,children's cancer institute australia for medical research,randwick,new south wales, Australia, the walter and eliza hall institute of medical research,parkville,victoria,australia,departments of neurology,brigham and women's hospital and harvard medical school,boston,massachusetts, United States, the walter and eliza hall institute of medical research,parkville,victoria,australia,department of medical biology,university of melbourne,parkville,victoria, Australia, the walter and eliza hall institute of medical research,parkville,victoria,australia,department of medical biology,university of melbourne,parkville,victoria, Australia, the walter and eliza hall institute of medical research,parkville,victoria,australia,department of medical biology,university of melbourne,parkville,victoria, Australia, the walter and eliza hall institute of medical research,parkville,victoria,australia,department of medical biology,university of melbourne,parkville,victoria, Australia
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Authors
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