Academic Journal
SYK ubiquitination by CBL E3 ligases restrains cross-presentation of dead cell-associated antigens by type 1 dendritic cells.
| العنوان: | SYK ubiquitination by CBL E3 ligases restrains cross-presentation of dead cell-associated antigens by type 1 dendritic cells. |
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| المؤلفون: | Conor M Henry, Carlos A Castellanos, Michael D Buck, Evangelos Giampazolias, Bruno Frederico, Ana Cardoso, Neil C Rogers, Oliver Schulz, Sonia Lee, Johnathan Canton, Peter Faull, Ambrosius P Snijders, Bhopal Mohapatra, Hamid Band, Caetano Reis e Sousa |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Immunology, Computational & Systems Biology, Model organisms, Biochemistry & Proteomics, Tumour Biology, Chemical Biology & High Throughput, Infectious Disease, anti-tumor immunity, CBL E3 ligase, CD8(+) T cells, CP: Immunology, cross-presentation, cross-priming, dendritic cells, DNGR-1/CLEC9A, spleen tyrosine kinase, SYK, Reis e Sousa CC2090, PRT, Skehel, Mark, BRF-ack, FC-ack, 0601 Biochemistry and Cell Biology, 1116 Medical Physiology, 31 Biological sciences |
| الوصف: | Cross-presentation of dead cell-associated antigens by conventional dendritic cells type 1 (cDC1s) is critical for CD8+ T cells response against many tumors and viral infections. It is facilitated by DNGR-1 (CLEC9A), an SYK-coupled cDC1 receptor that detects dead cell debris. Here, we report that DNGR-1 engagement leads to rapid activation of CBL and CBL-B E3 ligases to cause K63-linked ubiquitination of SYK and terminate signaling. Genetic deletion of CBL E3 ligases or charge-conserved mutation of target lysines within SYK abolishes SYK ubiquitination and results in enhanced DNGR-1-dependent antigen cross-presentation. We also find that cDC1 deficient in CBL E3 ligases are more efficient at cross-priming CD8+ T cells to dead cell-associated antigens and promoting host resistance to tumors. Our findings reveal a role for CBL-dependent ubiquitination in limiting cross-presentation of dead cell-associated antigens and highlight an axis of negative regulation of cDC1 activity that could be exploited to increase anti-tumor immunity. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://figshare.com/articles/journal_contribution/SYK_ubiquitination_by_CBL_E3_ligases_restrains_cross-presentation_of_dead_cell-associated_antigens_by_type_1_dendritic_cells_/24721167 |
| DOI: | 10.25418/crick.24721167.v1 |
| الاتاحة: | https://doi.org/10.25418/crick.24721167.v1 https://figshare.com/articles/journal_contribution/SYK_ubiquitination_by_CBL_E3_ligases_restrains_cross-presentation_of_dead_cell-associated_antigens_by_type_1_dendritic_cells_/24721167 |
| Rights: | CC BY 4.0 |
| رقم الانضمام: | edsbas.6A0FD95B |
| قاعدة البيانات: | BASE |
| DOI: | 10.25418/crick.24721167.v1 |
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