Selective autophagy of the adaptor protein Bcl10 modulates T cell receptor activation of NF-κB.

The 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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Autophagy, Caspases, Cell Differentiation, Cytosol, Gene Expression Regulation, Heat-Shock Proteins, Homeostasis, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Microscopy, Confocal, NF-kappa B, Neoplasm Proteins, Phagosomes, Protein Interaction Mapping, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocyte Subsets, Th2 Cells, Ubiquitin-Conjugating Enzymes
Immunity
Date: Jun. 29, 2012
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