| First Author | Paul S | Year | 2012 |
| Journal | Immunity | Volume | 36 |
| Issue | 6 | Pages | 947-58 |
| PubMed ID | 22658522 | Mgi Jnum | J:187308 |
| Mgi Id | MGI:5436180 | Doi | 10.1016/j.immuni.2012.04.008 |
| Citation | Paul S, et al. (2012) Selective autophagy of the adaptor protein Bcl10 modulates T cell receptor activation of NF-kappaB. Immunity 36(6):947-58 |
| abstractText | The adaptor protein Bcl10 is a critically important mediator of T cell receptor (TCR)-to-NF-kappaB signaling. Bcl10 degradation is a poorly understood biological phenomenon suggested to reduce TCR activation of NF-kappaB. 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-kappaB 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-kappaB. Together, these data demonstrate that selective autophagy of Bcl10 is a pathway-intrinsic homeostatic mechanism that modulates TCR signaling to NF-kappaB in effector T cells. This homeostatic process may protect T cells from adverse consequences of unrestrained NF-kappaB activation, such as cellular senescence. |
