Cutting Edge: Selective Role of Ubiquitin in MHC Class I Antigen Presentation
| Autor: | Laurence C. Eisenlohr, Julie M. Marvin, Nia Tatsis, Lan Huang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Small interfering RNA
Ovalbumin Immunology Vaccinia virus Biology Article Mice Ubiquitin MHC class I Immunology and Allergy Animals Ubiquitins chemistry.chemical_classification DNA ligase Gene knockdown Antigen Presentation Antigen processing MHC class I antigen Endoplasmic reticulum Histocompatibility Antigens Class I H-2 Antigens Ubiquitination Molecular biology Recombinant Proteins chemistry biology.protein Peptides Chickens |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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