| First Author | Leverrier S | Year | 2011 |
| Journal | Cell Death Differ | Volume | 18 |
| Issue | 1 | Pages | 90-8 |
| PubMed ID | 20523353 | Mgi Jnum | J:186349 |
| Mgi Id | MGI:5432071 | Doi | 10.1038/cdd.2010.69 |
| Citation | Leverrier S, et al. (2011) Enzymatically active single chain caspase-8 maintains T-cell survival during clonal expansion. Cell Death Differ 18(1):90-8 |
| abstractText | The extrinsic, or death receptor, pathway integrates apoptotic signals through the protease caspase-8 (casp8). Beyond cell death regulation, non-apoptotic functions of casp8 include its essential requirement for hematopoiesis and lymphocyte clonal expansion, and tempering of autophagy in T cells. However, the mechanistic basis for the control of these disparate cellular processes remains elusive. Here, we show that casp8-deficient T-cell survival was rescued by enzymatically active, but not inactive, casp8-expressing retroviruses. The casp8 catalytic induction in proliferating T cell occurred independent of extrinsic and intrinsic apoptotic-signaling cascades and did not induce casp8 proteolytic processing. Using a biotinylated probe selectively targeting enzymatically active caspases, catalytically active full-length casp8 was found in vivo in dividing T cells. A casp8 D387A processing mutant was able to rescue casp8-deficient T-cell proliferation, validating that casp8 self-processing is not required for its non-apoptotic function(s). Finally, casp8 activity was highest in CD8(+) T cells, the most rapidly proliferating subset. These results show that the catalytically competent form of casp8 is required for rapid T-cell proliferation in response to TCR ligation, but that processing of the caspase is only necessary to promote apoptosis. |
