Selective Autophagy of the Adaptor Protein Bcl10 Modulates T cell Receptor Activation of NF- κB

Suman Paul et al. 2012. Immunity 36, 947-958

Speaker: Kai-Fei Chang (張凱斐)                                 Time: 14:00~15:00, Nov. 14, 2012

Commentator: Dr. Chih-Peng Chang (張志鵬老師)    Place: Room 601

Abstract

After binding of T cell receptor (TCR) to MHC-peptide complex on an antigen presenting cell, T cell is activated for proliferation and differentiation.  TCR signaling activates NF-κB to drive downstream gene expression.   Bcl10 is an adaptor protein involved in TCR downstream signaling pathway to regulate the activation of NF-κB.  When TCR signaling is activated, Bcl10 puncta can be detected in the cytoplasm¹.  Autophagy has been suggested to be a cell survival mechanism for degrading unfolded and aggregated proteins.  Previous studies have shown that T cell activation triggers autophagy and degradation of Bcl10^2,3.  In this article, the authors found that Bcl10 formed cytosolic punctate structures after stimulation of TCR signaling.  Colocalization of Bcl10 and autophagosomes was detected in activated T cells, followed by the degradation of Bcl10 inautophagosomes.  p62, an adaptor protein during autophagy, has been demonstrated to recognize polyubiquitinated proteins for degradation.   Following TCR stimulation, p62 bound to polyubiquitinated Bcl10 and then targeted Bcl10 to autophagosome.  Moreover, the authors identified thatlysines 31 and 63 were essential for the degradation and polyubiquitination of Bcl10.  In autophagy-defective T cells, NF-κB activation and CD25 expression were enhanced after TCR stimulation.  In conclusion, following TCR activation, Bcl10 is degraded via autophagy for down-regulation of NF-κB signal pathway.

References:

1.      Rossman, J.S., Stoicheva, N.G., Langel, F.D., Patterson, G.H., Lippincott- Schwartz, J., and Schaefer, B.C. (2006). POLKADOTS are foci of functional interactions in T-cell receptor-mediated signaling to NF-κB. Mol. Biol. Cell 17, 2166–2176.

2.      Scharschmidt, E., Wegener, E., Heissmeyer, V., Rao, A., and Krappmann, D. (2004). Degradation of Bcl10 induced by T-cell activation negatively regulates NF-κB signaling. Mol. Cell. Biol. 24, 3860–3873.

3.      Li, C., Capan, E., Zhao, Y., Zhao, J., Stolz, D., Watkins, S.C., Jin, S., and Lu, B. (2006). Autophagy is induced in CD4⁺ T cells and important for the growth factor-withdrawal cell death. J. Immunol. 177, 5163–5168.