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

ABSTRACT: The adaptor protein Bcl10 is a critically important mediator of T cell receptor (TCR)-to-NF-?B signaling. Bcl10 degradation is a poorly understood biological phenomenon suggested to reduce TCR activation of NF-?B. 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-?B 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-?B. Together, these data demonstrate that selective autophagy of Bcl10 is a pathway-intrinsic homeostatic mechanism that modulates TCR signaling to NF-?B in effector T cells. This homeostatic process may protect T cells from adverse consequences of unrestrained NF-?B activation, such as cellular senescence.

SUBMITTER: Paul S 

PROVIDER: S-EPMC3389288 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature