| First Author | Hinshaw-Makepeace J | Year | 2008 |
| Journal | Eur J Immunol | Volume | 38 |
| Issue | 1 | Pages | 54-63 |
| PubMed ID | 18081036 | Mgi Jnum | J:130528 |
| Mgi Id | MGI:3771878 | Doi | 10.1002/eji.200636956 |
| Citation | Hinshaw-Makepeace J, et al. (2008) c-FLIP(S) reduces activation of caspase and NF-kappaB pathways and decreases T cell survival. Eur J Immunol 38(1):54-63 |
| abstractText | Effective stimulation of NF-kappaB in T cells following TCR ligation requires the activity of caspase-8. The active caspase-8 complex includes the paracaspase, MALT1, and Bcl-10, which connect to the NF-kappaB pathway. It has been less clear what regulates the level of caspase-8 activity during T cell activation. A likely candidate is cellular FLIP (c-FLIP), an enzymatically inert caspase-8 homologue. Two alternatively spliced forms of c-FLIP exist, a long form (c-FLIP(L)) and a short-form (c-FLIP(S)). The latter lacks the C-terminal caspase-like domain. c-FLIP(L) can heterodimerize with and activate caspase-8 through an activation loop in the C terminus of c-FLIP(L). Here we show that, in contrast to c-FLIP(L), c-FLIP(S) inhibits activation of caspase-8 in T cells, and consequently reduces recruitment of MALT1 and Bcl-10 to the active caspase complex. This results in reduced activity of NF-kappaB. Consequently, T cells from c-FLIP(S)-transgenic mice undergo more rapid cell death both spontaneously and after activation. The findings suggest that c-FLIP(S) functions to reduce the expansion of T cells during an immune response. |
