| First Author | Rios KE | Year | 2020 |
| Journal | Cell Immunol | Volume | 356 |
| Pages | 104179 | PubMed ID | 32763502 |
| Mgi Jnum | J:307276 | Mgi Id | MGI:6720225 |
| Doi | 10.1016/j.cellimm.2020.104179 | Citation | Rios KE, et al. (2020) CARD19, the protein formerly known as BinCARD, is a mitochondrial protein that does not regulate Bcl10-dependent NF-kappaB activation after TCR engagement. Cell Immunol 356:104179 |
| abstractText | After T cell receptor (TCR) engagement, the CARD11-Bcl10-Malt1 (CBM) complex oligomerizes to transduce NF-kappaB activating signals. Bcl10 is then degraded to limit NF-kappaB activation. The cDNA AK057716 (BinCARD-1) was reported to encode a novel CARD protein that interacts with Bcl10 and modestly inhibits NF-kappaB activation. In a later study, a second isoform, BinCARD-2, was identified. Here, we report that the cDNA AK057716 (BinCARD-1) is an incompletely spliced derivative of the gene product of C9orf89, whereas CARD19 (BinCARD-2) represents the properly spliced isoform, with conservation across diverse species. Immunoblotting revealed expression of CARD19 in T cells, but no evidence of BinCARD-1 expression, and microscopy demonstrated that endogenous CARD19 localizes to mitochondria. Although we confirmed that both BinCARD-1 and CARD19 can inhibit NF-kappaB activation and promote Bcl10 degradation when transiently overexpressed in HEK293T cells, loss of endogenous CARD19 expression had little effect on Bcl10-dependent NF-kappaB activation, activation of Malt1 protease function, or Bcl10 degradation after TCR engagement in primary murine CD8 T cells. Together, these data indicate that the only detectable translated product of C9orf89 is the mitochondrial protein CARD19, which does not play a discernible role in TCR-dependent, Bcl10-mediated signal transduction to Malt1 or NF-kappaB. |
