Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Immunity. 2012 Jun 29;36(6):947-58. doi: 10.1016/j.immuni.2012.04.008. Epub 2012 May 31.

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

Author information

  • 1Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD 20814, USA.

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

Comment in

PMID:
22658522
[PubMed - indexed for MEDLINE]
PMCID:
PMC3389288
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk