Cutting Edge: Selective Role of Ubiquitin in MHC Class I Antigen Presentation
Cutting Edge: Selective Role of Ubiquitin in MHC Class I Antigen Presentation
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DOI：
10.4049/jimmunol.1003411
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发表时间：
2011-02-15
影响因子：
4.4
通讯作者：
Eisenlohr, Laurence C.
中科院分区：
文献类型：
--
作者：
Huang, Lan;Marvin, Julie M.;Eisenlohr, Laurence C.
The importance of ubiquitination in MHC class I-restricted Ag processing remains unclear. To address this issue, we overexpressed wild-type and dominant-negative lysineless forms of ubiquitin (Ub) in mammalian cells using an inducible vaccinia virus system. Overexpression of the lysineless Ub nearly abrogated polyubiquitination and potently inhibited epitope presentation from a cytosolic N-end rule substrate as well as endoplasmic reticulum (ER)-targeted model Ags. In contrast, there was little impact on Ag presentation from cytosolic proteins. These trends were location dependent; redirecting cytosolic Ag to the ER rendered presentation lysineless Ub-sensitive, whereas retargeting exocytic Ag to the cytosol had the inverse effect. This dichotomy was further underscored by small interfering RNA knockdown of the ER-associated Ub ligase Hrd1. Thus, Ub-dependent degradation appears to play a major role in the MHC class I-restricted processing of ER-targeted proteins and a more restricted role in the processing of cytosolic proteins. The Journal of Immunology, 2011, 186: 1904-1908.
