Caspase enzyme activity is not essential for apoptosis during thymocyte development.
作者： Petra Doerfler , Katherine A. Forbush , Roger M. Perlmutter
DOI: 10.4049/JIMMUNOL.164.8.4071
关键词: Apoptosis 、 Cell biology 、 NLRP1 、 Thymocyte 、 Caspase 、 Caspase 2 、 Molecular biology 、 Biology 、 Signal transduction 、 Fas receptor 、 Caspase 3
摘要: Caspases, a family of cysteine proteases, are critical mediators apoptosis. To address the importance caspases in thymocyte development, we have generated transgenic mice that express baculovirus protein p35, viral caspase inhibitor, specifically thymus. p35 expression inhibited Fas (CD95)-, CD3-, or peptide-induced activity vitro and conferred resistance to Fas-induced However, did not block specific negative selection OT1 HY TCR mouse models. Even potent pharmacological inhibitor zVAD-FMK (benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone) could prevent deletion thymocytes, although it improved basal survival vitro. Moreover, developmental observed rag1-/- which lack pre-TCR signaling, was also rescued by expression. These results indicate caspase-independent signal transduction pathways can mediate death during normal T cell development.
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