Selective Autophagy of the Adaptor Protein Bcl10 Modulates T Cell Receptor Activation of NF-κB
| Autor: | Anuj K. Kashyap, You-Wen He, Suman Paul, Wei Jia, Brian C. Schaefer |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Sequestosome-1 Protein
Cellular differentiation Immunology Receptors Antigen T-Cell Autophagy-Related Proteins Biology Lymphocyte Activation T-Cell Receptor Activation Article Mice 03 medical and health sciences Cytosol Th2 Cells 0302 clinical medicine T-Lymphocyte Subsets Phagosomes Protein Interaction Mapping Autophagy Animals Homeostasis Immunology and Allergy Heat-Shock Proteins Adaptor Proteins Signal Transducing 030304 developmental biology 0303 health sciences Microscopy Confocal Effector T-cell receptor NF-kappa B Signal transducing adaptor protein Cell Differentiation B-Cell CLL-Lymphoma 10 Protein Neoplasm Proteins Cell biology Mice Inbred C57BL Infectious Diseases Gene Expression Regulation Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein Caspases 030220 oncology & carcinogenesis Ubiquitin-Conjugating Enzymes Cancer research Signal transduction Signal Transduction |
| Zdroj: | Immunity. 36(6):947-958 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2012.04.008 |
| Popis: | SummaryThe adaptor protein Bcl10 is a critically important mediator of T cell receptor (TCR)-to-NF-κB signaling. Bcl10 degradation is a poorly understood biological phenomenon suggested to reduce TCR activation of NF-κB. Here we have shown that TCR engagement triggers the degradation of Bcl10 in primary effector T cells but not in naive T cells. TCR engagement promoted K63 polyubiquitination of Bcl10, causing Bcl10 association with the autophagy adaptor p62. Paradoxically, p62 binding was required for both Bcl10 signaling to NF-κB and gradual degradation of Bcl10 by autophagy. Bcl10 autophagy was highly selective, as shown by the fact that it spared Malt1, a direct Bcl10 binding partner. Blockade of Bcl10 autophagy enhanced TCR activation of NF-κB. Together, these data demonstrate that selective autophagy of Bcl10 is a pathway-intrinsic homeostatic mechanism that modulates TCR signaling to NF-κB in effector T cells. This homeostatic process may protect T cells from adverse consequences of unrestrained NF-κB activation, such as cellular senescence. |
| Databáze: | OpenAIRE |
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