Selective autophagy of the adaptor protein Bcl10 modulates T cell receptor activation of NF-κB.
Immunity
; 36(6): 947-58, 2012 Jun 29.
Article
em En
| MEDLINE
| ID: mdl-22658522
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Receptores de Antígenos de Linfócitos T
/
Subpopulações de Linfócitos T
/
NF-kappa B
/
Proteínas Adaptadoras de Transdução de Sinal
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article