Role for ribosome-associated quality control in sampling proteins for MHC class I-mediated antigen presentation
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- Débora Broch Trentini
- Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
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- Matteo Pecoraro
- Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
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- Shivani Tiwary
- Computational Systems Biochemistry Research Group, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
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- Jürgen Cox
- Computational Systems Biochemistry Research Group, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
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- Matthias Mann
- Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
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- Mark S. Hipp
- Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
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- F. Ulrich Hartl
- Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany;
抄録
<jats:p>Mammalian cells present a fingerprint of their proteome to the adaptive immune system through the display of endogenous peptides on MHC-I complexes. MHC-I−bound peptides originate from protein degradation by the proteasome, suggesting that stably folded, long-lived proteins could evade monitoring. Here, we investigate the role in antigen presentation of the ribosome-associated quality control (RQC) pathway for the degradation of nascent polypeptides that are encoded by defective messenger RNAs and undergo stalling at the ribosome during translation. We find that degradation of model proteins by RQC results in efficient MHC-I presentation, independent of their intrinsic folding properties. Quantitative profiling of MHC-I peptides in wild-type and RQC-deficient cells by mass spectrometry showed that RQC substantially contributes to the composition of the immunopeptidome. Our results also identify endogenous substrates of the RQC pathway in human cells and provide insight into common principles causing ribosome stalling under physiological conditions.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 117 (8), 4099-4108, 2020-02-11
Proceedings of the National Academy of Sciences
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キーワード
詳細情報 詳細情報について
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- CRID
- 1360017286656221184
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- ISSN
- 10916490
- 00278424
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- データソース種別
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- Crossref