MHC class I ubiquitination by a viral PHD/LAP finger protein

被引:169
作者
Boname, JM [1 ]
Stevenson, PG [1 ]
机构
[1] Univ Cambridge, Dept Pathol, Div Virol, Cambridge CB2 1QP, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
D O I
10.1016/S1074-7613(01)00213-8
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The murine gamma -herpesvirus-68 K3 (MK3) is a PHD/LAP finger protein that downregulates major histocompatibility complex (MHC) class I expression. In transfected cell lines, MK3 was expressed in the endoplasmic reticulum (ER) membrane, where it bound the cytoplasmic tail of newly synthesized H-2D(b) glycoproteins and targeted them for degradation. Proteasome inhibitors blocked the degradation and led to an accumulation of ubiquitinated H-2D(b). Because this retained its native conformation, ubiquitination preceded any denaturation or dislocation to the cytosol. The PHD/LAP finger of MK3 was not required for H-2D(b) binding but was essential for its ubiquitination and degradation. Thus, gamma -herpesviruses have adapted the cellular PHD/LAP motif to immune evasion, apparently for the catalysis of MHC class I ubiquitination.
引用
收藏
页码:627 / 636
页数:10
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